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REPAIR MANUAL - Euromachines

REPAIRMANUAL

NEW HOLLAND

VL570 VM370

VL610 VM460

VL620

VL630

VL640

VL660


SPECIFICATIONS

Chapter 1

CONTENT

Section Description Page

identification 3

..........................................................

Machine

4

...................................................................

Dimensions

machine technical specifications 6

...................................

Self--propelled

equipment technical specifications 9

.....................................

Harvesting

604 82 321 00 -02 - 2005


2 SPECIFICATIONS

604 82 321 00 -02- 2005


SPECIFICATIONS 3

MACHINE IDENTIFICATION DATA

Model Type Serial number Machine number

VL 660 664 001 001

VL 640 660 001 001

VL 630 660 001 001

VL 620 656 001 001

VL 610 656 001 001

VM 460 636 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

657 001 001

637 001 001

VL 570 655 001 001

VM 370 633 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

A = Manufacturer’s label

B = Stamped frame number

VL 610 ÷ 660 and VM 460: 604801000 (GB)

VL 570 and VM 370: 604801300 (GB)

Reference:

654 001 001

634 001 001

OPERATOR’S MANUAL

SPARE PART CATALOGUE

604 82 321 00 -02 - 2005


4 SPECIFICATIONS

604 82 321 00 -02- 2005

2100 litres

2600 litres

3200 litres


SPECIFICATIONS 5

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Code DIMENSIONS (mm)

H1 Height: without cab

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3810 3810

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 2000 to 2600

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 2600 l

HB5 Height under clearance hoppers, 3200 l

E Wheelbase 2860

La1 Max. width at the hoppers hoppers, 2100 l 2500/2300

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

2100 l + cab 3000/2800

2600 l or 3200 l 3000

self--propelled

Only

machine

self--propelled

Only

machine

2590 2390

2830 2630

LaB1 Hopper width 2100 l 2500 2300

2600 l

LaB2

l 3200

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 + Gb = La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 28

420/85

Tyres

R 28

480/70

Tyres

R 28

540/65

to front wheels Tyres

next

R 24

420/70

3000

3000

2800

2160 + 454 = 2614 1790 + 454 = 2244

2260 + 480 = 2740 1860 + 480 = 2340

2340 + 540 = 2880

Tyres 600x55x30.5 2360 + 600 = 2960

1930 + 420 = 2350 1730 + 420 = 2150

(V2 + Gb = La AV) Tyres 13.6 R 24 1930 + 350 = 2280 1730 + 350 = 2150

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

without cab 5390

with cab 5500 (5650)

DAV1 Front offset: without cab 910

DAV2 with cab 1050

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

604 82 321 00 -02 - 2005


6 SPECIFICATIONS

604 82 321 00 -02- 2005

1800 litres

2400 litres or 2200 litres


SPECIFICATIONS 7

COMMERCIAL DESCRIPTION VL 570 VM 370

Code DIMENSIONS (mm)

H1 Height: without cab 3160 3040

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3600 3420

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 1800 to 2300 from 1950 to 2450

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 1800 l

HB5 Height under clearance hoppers, 2400 l

E Wheelbase 2730

La1 Max. width at the hoppers hoppers, 2400 l

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

l + cab

2400 l +cab

2400

self--propelled

Only

machine

self--propelled

Only

machine

2540 2340

2750 2540

LaB1 Hopper width 1800 l 2500 2300

2200 l

LaB2

l 2800

2400

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 +Gb=La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 24

420/70

Tyres

R 24

480/65

Tyres

R 24

460/70

Tyres

R 24

340/85

Tyres 11.2R24

to front wheels Tyres

next

R 20

280/70

+ Gb = La AV) Tyres

(V2

R 20

320/70

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

DAV1 Front offset: without cab

DAV2 with cab

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

2065 + 431 = 2496

2095 + 484 = 2579

2095 + 462 = 2557

2800

1975 + 366 = 2341 1775 + 366 = 2141

1755 + 291 = 2046

1694 + 275 = 1969

1942 + 315 = 2257 1742 + 315 = 2057

without cab 4910 (5110)

with cab 4980 (5180)

604 82 321 00 -02 - 2005


8 SPECIFICATIONS

WEIGHT

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

PTAC Total allowed weight under load (kg) 9500

Partition front axle (kg)

rear axle (kg)

4200

5300

weight with harvest- Total 8700 (9200)

Empty weight with harvest Total 8700 (9200)

Empty

equipment and without

g q p ing

(with) destemmers

Weight of one wheel (kg) 420/70 R 24

Thermal engine weight (kg)

FEEDING/EXHAUST

480/70 R 28

540/65 R 28

Fuel tank Used fuel

Capacity (litres)

Diesel oil

Engine feeding system Direct injection

Air filter Make

Type

Engine cooling Water capacity (litres)

250

DONALDSON

ELB 12--0265

Fan Sucking

Cooling fan ∅ (mm) 610 584

DRIVE

Pump for engine fan Make

Displacement (cm�/rev.)

Empty operating speed

(rpm)

Capacity (l/minute), output

0.9

Fan motor Make

Variable flow inching hy-

draulic pump:

Displacement (cm�/rev.)

Make

Type

Total displacement

(cm�/rev.)

SAUER

17

(1.02 x engine speed)

35

SAUER

12.2

REXROTH

A4VG

from 0 to 105


DRIVE (follows)

SPECIFICATIONS 9

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Priming pump Displacement (cm�/rev.)

Capacity (l/minute), output

0.9

Front wheel motor Make

Type

Rear wheel motor Make

Displacement (cm�/rev.)

Type

Displacement (cm�/rev.)

26

57.3

POCLAIN

MS 08

1043

POCLAIN

MSE 18

2636 (1406/1230)

Max. speed (km/h) in road position 25 km/h

Max. speed (km/h) in field position 12

Hydraulic oil

Capacity l/minute

Oil type

Extractor pump and con-

veyors

Shaking

pump

Steering/lifting/hopper pump

Total

Reservoir 65

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

NEW HOLLAND: Hydrosystem 68

Hydrosystem 68 BIO S

REXROTH

”Load sensing” from 0 to 45

2500 (see engine speed)

101.2

SAUER

22

2500 (see engine speed)

50

SAUER

14

(1.02 x engine speed)

STEERING Hydrostatic

Type EATON QAMP 146 cm�/rev.

BRAKING

Service brake Supplied by the hydrostatic transmission

Parking brake (acting on the two rear wheels) Operated by ONE pedal and by the steering

Parking brake Operated by left manual lever

29

604 82 321 00 -02 - 2005


10 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

TILTING CORRECTION 30%

PLATFORM CAB

Heated and air--conditioned cab Depending on the model

Activated charcoal filter Option

On--board computer �

Grand--Luxe seat

Pneumatic seat �

Multi--function lever �

LIGHTING AND WARNING LIGHTS

High/low beams 2

Front parking lights 2

Rear parking lights 2

Direction indicator warning lights Front

Rear

Side

Stop lights 2

License plate light 1

Reflector Rear 2

Revolving beacon with cab 2

Supply voltage / battery 12 V / 180 Ah

Alternator 120 A

2

2

2


HARVESTING EQUIPMENT

HARVESTING HEADER

SPECIFICATIONS 11

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Type Swinging, self--aligning

System Shaking, SDC

Number of shakers 14

Straight/elbow connecting rod 13/1

Shaking drive Motor manufacturer

Displacement (cm�/rev.)

ECU:

Ratio

Toe--in adjustable from the operator’s seat

Grease: TUTELA MRM2

SAUER

Amplitude settings 4

22

4/1

2.7 kg

Min. clearance under the frame (mm) 2000

Grape harvesting useful height (mm) 1650

Harvesting tunnel width (mm) 500

604 82 321 00 -02 - 2005


12 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

RECEIVING/TRANSPORTATION

Noria system Buckets per chain

Type

Synchronized

63/61

XXL/small

in field speed

Width of flexible stock guides (mm) from195to265

Tightness length (mm) 2100

Harvesting min. height (mm) 150

Drive Motor manufacturer

Harvesting conveyors Width (mm)

Displacement (cm�/rev.)

Max. operating speed rpm

Reverse

Single operation Motor manufacturer

Displacement (cm�/rev.)

EATON

500

600

about 750

yes

EATON

31.6


CLEANING

SPECIFICATIONS 13

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

2 upper extractors with removable

stalk choppers

2 lower extractors with

2 independent stalk choppers, en-

abled by shaking

HOPPERS

Diameter (mm)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Diameter

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Direction of rotation

460

hydraulic

SAUER

11

430

Hydraulic system

SAUER

6

Hydraulic system

EATON

8.2

reverse to the wheels

Capacity 2 x 1600

2 x 1300

2 x 1050

Electrically--operated distribution auger Control independent of the grape harvester

604 82 321 00 -02 - 2005


14 SPECIFICATIONS

604 82 321 00 -02- 2005


WEIGHT

SPECIFICATIONS 15

COMMERCIAL DESCRIPTION VL 570 VM 370

PTAC Total allowed weight under load (kg)

Partition front axle (kg)

Empty weight with

harvesting equipment

and without (with)

destemmers

Weight of one wheel

(kg)

rear axle (kg)

Total

Thermal engine weight (kg)

FEEDING/EXHAUST

Fuel tank Capacity 160 litres * *

4--cylinder engine --

-- ISO power (KW/CV)

-- Displacement = 1125 cm 3 /cylinder

Air filter Make

Type

Engine cooling Liquid capacity (litres)

Fan

94/128

Air/air intercooler * *

DRIVE

Variable displace-

ment inching hy-

draulic pump:

”Rexroth” A4VG90

Displacement elimin-

ation:

Drive:

Total displacement

90 cm�/rev.

*

*

electr.

*

94/128

*

*

electr.

*

604 82 321 00 -02 - 2005


16 SPECIFICATIONS

DRIVE (follows)

COMMERCIAL DESCRIPTION VL 570 VM 370

Priming pump Displacement 25 cm�/rev.

604 82 321 00 -02- 2005

Capacity (l/minute), output

0.9

Front wheel motor Make ”Poclain”

Type MSE 05

Displacement 688 cm�/rev.

Rear wheel motor Make ”Poclain”

Type MSE 11

Displacement 843/843

cm�/rev.

* *

Double steering valve * *

Front drive wheels in road position * *

”Twin lock” antiskid * *

Torque reduction on front wheels, optional * *

Max. speed in road position, 25 km/h * *

Max. speed in field position, 12 km/h * *

Hydraulic oil

Capacity l/minute

Oil type

Total

Reservoir, 65 litres

New Holland

Hydrosystem 68

Hydraulic filtering (intake/return) * *

Extractor pump and

conveyors

Shaking

pump

Make ”Sauer”

Displacement 44 cm�/rev.

Idle operating rpm speed =

engine

Capacity (l/minute), output

0.9

Make ”Sauer”, double

Displacement 22 cm�/rev.

Idle operation rpm speed =

93% of engine speed

Capacity (l/minute), output

0.9

*

*

*

*

*

*

*

*

*

*

*

*


SPECIFICATIONS 17

COMMERCIAL DESCRIPTION VL 570 VM 370

Steering/lifting/hopper

pump

STEERING

Make ”Sauer”, double

Displacement 11 cm�/rev.

Idle operation rpm speed

= 93% of engine speed

Capacity (l/minute), output

0.9

Type: ”Eaton” valve, 100 cm 3 /rev. * *

BRAKING

Hydrostatic service brake * *

Parking brake (acting on the two rear wheels) * *

Manually--operated parking brake, on the left * *

Electrically--operated independent brakes No No

*

*

604 82 321 00 -02 - 2005


18 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

TILTING CORRECTION

Max. tilting (%) 25 25

Max. tilting in road position (%) 8 8

Max. tilting in work position (%)

(with destemmers or special implement and

front wheels with ballasts)

FRAME

604 82 321 00 -02- 2005

32 32

Harvesting header quick uncoupling * *

Link fitting possibility * *

Front and rear tracks = see relevant SB * *

PLATFORM CAB

Heated and air--conditioned cab

Activated charcoal filter

ELTEC control panel * *

Imitation leather seat as standard outfit * *

Pneumatic seat, with cab, optional * *

Multifunction lever, number of push buttons 18 18

Electrical inching control, adjusted through

sensors (optional radar)

Electrical presetting for:

-- electrically--operated rear view mirrors

-- CDHA

-- rear viewing

* *

*

*

*

*

*

*


SPECIFICATIONS 19

COMMERCIAL DESCRIPTION VL 570 VM 370

LIGHTING AND WARNING LIGHTS

High/low beams

Front parking lights

Rear parking lights

Direction indicator

warning lights

Stop lights

License plate light

Front

Rear

Side

Reflector Rear

Revolving beacons

Battery, capacity (AH) 135 135

Alternator -- 120 A * *

604 82 321 00 -02 - 2005


20 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

HARVESTING EQUIPMENT

HARVESTING HEADER

Harvesting header hour counter yes yes

Type -- swinging, self--aligning * *

SDC shaking system * *

Number of shakers 14 12

Straight/elbow flexible connecting rod 13/1 11/1

Shaking drive ”Sauer/Eaton” motor

Toe--in adjustable

from the operator’s

seat

604 82 321 00 -02- 2005

Displacement

(cm�/rev.)

Reducer control unit:

1/4

Grease: GR75MD

22

*

22

* *

Amplitude settings 3 3

Removable shakers, optional * *

Min. clearance under the frame

1950/2450 mm

Min. clearance under the frame

1800/2300 mm

Grape harvesting useful height (mm) 1050 900

Harvesting tunnel

width (mm)

RECEIVING/TRANSPORTATION

Noria system Large buckets

Small buckets

Fastening by 2 plates

Drive gears:

16/59

17/58

Width of flexible stock guides (mm) 195/265 165/235

Tightness length 1750 mm * *

Min. harvesting height 150 mm * *

Operation ”Eaton” motor

Displacement 395

cm�/rev.

*

55

*

*

*

*

53

* *

*


SPECIFICATIONS 21

COMMERCIAL DESCRIPTION VL 570 VM 370

Harvesting con-

veyors

Width 450 mm

Max. operating speed

rpm

Reverse

Single operation ”Eaton” motor

CLEANING

2 upper extractors

with removable

stalk choppers

2 lower extractors

(optional)

2 independent stalk

choppers, enabled

by noria in propor-

tional

HOPPERS

Capacity

Displacement 31.6

cm�/rev.

Diameter 430 mm

”Sauer” motor

Displacement 11

cm�/rev.

Electrically--operated

speed

Diameter 430 mm

”Sauer” motor

Displacement

6cm�/rev.

Electrically--operated

speed

”Eaton” motor

Displacement

8.2 cm�/rev.

*

*

* *

1800 litres *

2360 litres *

Distribution auger

”Eaton” motor

Displacement

31.6 cm�/rev.

Adjustable speed

*

*

*

*

*

*

*

* *

*

*

*

*

*

604 82 321 00 -02 - 2005


22 SPECIFICATIONS

604 82 321 00 -02- 2005


Section Description

00 Maintenance

REPAIRMANUAL

CONTENT

05 Machine preparation and equipment

10 Engine

14 Live PTO

29 Hydrostatic transmission

33 Brakes & Controls

35 Hydraulic systems

36 Pneumatic systems

37 Towing hooks and ballasting

39 Frames

41 Steering

44 Wheels

50 Cab climate control

55 Electrical systems

58 Attachments/headers

60 Product feeding

74 Cleaning

80 Grape storage -- hoppers

88 Accessories

90 Platform, cab, bodywork and decals

1

604 82 321 00 -02 - 2005


2

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 1

SECTION 00 - MAINTENANCE

Chapter 1

CONTENT

Description Page

......................................................

Section

Capacities 2

....................................................................

00.000

engine maintenance 3

...................................................

Thermal

5

.....................................................................

Greasing

filter 8

................................................................

Hydraulic

9

.....................................................................

Washing

system maintenance 13

.................................................

Hydraulic

maintenance and winter storage 15

........................................

Routine

604 82 321 00 -02 - 2005


2 SECTION 00 - MAINTENANCE - CHAPTER 1

Item to be serviced

Self--propelled machine

greasers

604 82 321 00 -02- 2005

CAPACITIES

LUBRICANTS AND FLUIDS

Quantity

dm3 (litres)

Recommended

product

Grease

AMBRA GR 9

International

classification

Lithium--calcium based grease,

consistency NLGI 2

Harvesting machine greasers Grease 24 cartridges

Noria ECU 1 Food type re. 62777339

Shaking rear connecting rod

articulations

Shaking ECU 2.7 kg GR 75 MD

Engine sump and filter/s

6--cylinder engine

4--cylinder engine

15

9.5

Grease Teflon silicone grease

NH 720 A

Oil

AMBRA SUPER GOLD

HSP

15W - 40

Reservoir 65 Oil

AMBRA

HYDROSYSTEM 68

Cooling system 20 AMBRA

AGRIFLU (50%) +

Clean water (50%)

Sitef degree 3

410--g cartridge, re. 920019780

Re.: 661874

molybdenum bisulfide grease,

consistency NLGI 2

SAE 15W40

API CH -- 4

ACEA E3/E5

ISO 68

DIN 51524 -- part 2


a) After the first 50 hours

SECTION 00 - MAINTENANCE - CHAPTER 1 3

-- Let the engine run until it reaches the stan-

dard operating temperature.

-- Replace the diesel oil filter cartridge/s.

-- Check alternator and compressor belt ten-

sion.

-- Check engine tightness.

b) Every day or every ten hours, check:

-- the oil level,

-- the coolant level,

-- the radiator core cleanliness.

THERMAL ENGINE MAINTENANCE

c) Every 400 hours, or before each harvest-

ing season, replace:

-- the engine oil;

-- the oil filter cartridge/s;

-- the diesel oil filter cartridge/s;

-- Check belt tension.

-- Check the radiator core cleanliness.

-- If the air filter clogging indicator comes on,

clean the main cartridge by compressed

air, blowing inside out.

Be careful not to use a pressure over

6 bar; shift the nozzle downwards and hold

it at about 3 cm from the paper.

d) Only before each harvesting season:

-- replace the air filter main cartridge.

NOTE: the diesel oil filter cartridges should be re-

placed more often if the diesel oil conditions require

it.

604 82 321 00 -02 - 2005


4 SECTION 00 - MAINTENANCE - CHAPTER 1

14

20

13

19

10

E

F

604 82 321 00 -02- 2005

18

11

12

16

A B

1 2 3 4 5 6 7 8

17

15

10 11 12

19 20

9

13 14 15 16 17 18

D

C

1 2 3 4 5 6 7

8 9 10 11 12 13

14 15 16 17 18 19 20

4

6

2

8

1

3

5

7

VM 460

9

VL 610 ÷ 660


SECTION 00 - MAINTENANCE - CHAPTER 1 5

GREASING POINT POSITION - VL 610 ÷ 660 and VM 460

The greasing ramp is located on the harvesting

equipment central gangway. All these points must

be greased with food--type grease every day, after

washing.

A) Noria drive shaft

B) Shaking control shaft

C) Right shaking control connecting rod

D) Left shaking control connecting rod

E) Right shaking plate

F) Left shaking plate

There is no centralized greasing on the self--pro-

pelled machine, thus you need to grease daily only

the following:

-- 2 x 3 greasers on the front legs

HARVESTING EQUIPMENT

These positions are not localised and should be

greased every 50 hours:

� 2 x 2 greasers on the hopper cylinder axes

� 2 x 1 greaser on the lower stalk choppers

TOTAL: 26

SELF -PROPELLED MACHINE

To grease every 50 hours:

� 2 x 1 greaser on the steering cylinder pivot

� 2 x 2 greasers on the steering bar pivots

� 2 greasers on steering relay

� 2 x 2 greasers on the wheel link pivot

� 2 x 2 greasers on the rear lifting cylinder

TOTAL: 16

604 82 321 00 -02 - 2005


6 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 7

GREASING POINTS FOR VL 570 and VM 370

Position and number of greasers Greasing frequency

SELF -PROPELLED MACHINE

Front legs 2 x 3 6

10 h 50 h

Steering cylinder articulation 2

Steering relays 2

Steering bar ball joints 4

Rear wheel link articulation 2 x 2 4

Rear lifting cylinder articulation 2 x 2 4

Total 22

HARVESTING EQUIPMENT

Shaking front plate 2 x 2 4

Shaking control link rods 2 x 2 4

Right side shaking shaft bearing 1 1

Left side noria shaft bearing 1 1

Belt bearings 2x4 8

Hopper tilting cylinder 2x1 2

Hopper articulation 2x1 2

Harvesting equipment rear articulation 1 1

Lower stalk chopper 2 x 1 2

Total 25

604 82 321 00 -02 - 2005


8 SECTION 00 - MAINTENANCE - CHAPTER 1

Hydraulic filter cover

During reassembly, pay attention to the assembly

direction:

-- the A side with only one arrow on the cover

must be directed towards the return line;

-- the B side with two arrows on the cover must

be directed towards intake lines.

604 82 321 00 -02- 2005

A

B


To avoid the building up of sugar and dirt in the

harvesting equipment and to preserve the grape

harvesting quality, the machine must be washed

once or several times a day, and above all at the

end of the work.

The self--propelled machine washing must take

place with standstill thermal engine; anyway, for

cleaning the harvesting equipment in the best way,

it is necessary to start the norias, the conveyors

and the extractors, after having positioned the ma-

chine in a stable place. This is anyway a depar-

ture from the general safety requirements

specified in the Operator’s Manual.

This operation calls for close attention and strict

adherence to the following rules:

SECTION 00 - MAINTENANCE - CHAPTER 1 9

� first of all, this operation must be made by a

single operator, skilled in the control of this

machine.

� The machine should be placed in a stable

cleaning area, preferably on a level con-

crete floor measuring at least 5x8 m, pro-

vided with drainage facilities and consistent

with current environmental protection re-

gulations.

The cleaning area should be equipped with the

following:

� a hose with min. diameter 35 mm, long

enough to enable the washing all around the

machine;

� a sufficient flow of water to provide a 2--m jet,

or alternatively a heavy--duty pumping unit

with3to4m 3 capacity water storage tank;

� an adjustable nozzle to direct the water jet to

about 5 m;

� a ladder, 3.5--m high and a 0.7--m long hook.

NOTE: the use of a high pressure cleaning machine

is definitely not recommended.

WASHING THE MACHINE

PREPARING THE MACHINE FOR THE

WASHING AT THE END OF THE CAM-

PAIGN

Before emptying the last hoppers, stop the thermal

engine.

-- Getoffthedriver’sseatand,frominsidethe

harvesting machine, scroll the harvested prod-

uct gathered around the shaking plates and the

rear frame into the buckets.

-- Make an inspection all the machine round and,

starting from the ground, remove any impu-

rities or deposits sticking to the surfaces.

-- Climb onto the driver’s seat, start the thermal

engine, the extractors, the conveyors and the

norias in washing position. Run the engine for

10 seconds, then empty the hoppers.

604 82 321 00 -02 - 2005


10 SECTION 00 - MAINTENANCE - CHAPTER 1

After entering the washing area, lower the machine

to 10 cm from the ground and tilt the hoppers fully.

Make sure the inching lever is in neutral, engage

the hand brake, stop the thermal engine, get off

the tractor and position the hopper safety stops.

-- Place the ladder at the rear of the machine and

climb onto the rear arch. Using the hook, pull

off any vine shoots built up or sticking to and

around the plastic safety cover.

-- Shift the ladder and lay it against the pipe

where the side plates are fastened, so as to

release the elastics holding the plates and

make the residues behind fall down.

Make sure that the plate upper part folds

correctly against the lower one, to prevent

it from being trapped in the hoppers during

tilting.

This operation must be carried out on both ma-

chine sides.

-- Remove the ladder and the hopper stops.

-- Detach the elastics from the rear sealing plates

and remove any debris trapped behind.

-- Remove any plastic plugs sealing the lower

rear part of the norias.

-- Climb onto the driver’s seat and operate the

engine at medium speed, lower the hoppers,

engage the extractors and conveyors, then

place the norias in the washing position.

-- Get off the tractor, leaving the harvesting ma-

chine working parts in operation.

604 82 321 00 -02- 2005

WASHING (in the washing area)

this is a departure from

CAUTION:

general safety requirements specified in the

the

Operator’s Manual.

-- Open the water supply valve, pick up the hose

without the nozzle and climb onto the harvest-

ing machine operating platform located behind

the driver’s seat. From here, thoroughly wash

the top of the machine, the conveyors, the

hopper augers, the norias, etc. for about 10

minutes.

-- Get off the machine and, starting from the

ground, clean the inside of the tunnel from the

front of the harvesting machine:

� plates, shaking frame, shakers;

� then, inject water into the front LH and RH

baffles through the holes provided.

-- Now go to the back of the machine, open the

saloon doors and clean the rear part of the

harvesting machine tunnel:

� the shaking frame assembly, paying special

attention to the shaker connecting rods;

� the plates and the lower sealing sheets.

-- Inject water through the side openings in the

conveyor housings.

-- Sprayalotofwaterinthehoodsofthelower

extractors, remaining at a sufficient distance

from the stalk choppers.

the extractor rotors are

DANGER:

with stalk chopper knives.

fitted

Do not try and fit the pipe or the nozzle when the

thermal engine is running.


-- Now wash the rear outer part of the machine,

SECTION 00 - MAINTENANCE - CHAPTER 1 11

carefully cleaning the inside of the rear deflec-

tors. Inject water into the rear LH and RH de-

flectors through the holes provided.

-- Lay down the hose (shutting off the water sup-

ply, if necessary) and climb onto the tractor.

Raise the RH hopper for about 50 cm, just

enough to uncover the extractor intake hood.

-- Place the left hopper in the same position.

-- Increase the engine speed to maximum.

-- Get off the tractor, retrieve the hose and climb

onto the harvesting machine platform. Wash

the inside of the extractors by flooding them

with water, one after another, at 7--second in-

tervals.

-- Get off the harvesting machine platform, shut

off the water supply, climb onto the tractor and

stop the harvesting functions (extractors, con-

veyors and norias).

Option

At this stage you can check the extractor

chutes for cleanliness by opening the in-

spection doors provided. First make

sure that the stalk choppers have come

to a complete stop.

-- Operate the machine to empty the hoppers

and return to the washing area.

-- Raise the machine to mid--height and tilt the

hoppers completely, stop the thermal engine

and engage the parking brake.

-- Getoffthetractor,fitthenozzletothewater

hose and open the water supply. One side

after the other, direct the jet toward and around

each conveyor, paying special attention to the

lateral opening of the conveyor housings, to

the plates, etc...

-- From the back side of the machine, wash the

hoppers and the hopper auger ends.

� Inspect the machine again and wash the

wheel links, the wheels, the safety covers,

the lower extractor outlets, the cab, etc..

� Shut off the water supply and open the con-

veyor housing inspection doors through the

inside of the harvesting machine tunnel.

-- Climb onto the tractor, start the engine and set

it to idling. Lower the machine keeping the

hoppers lifted, start the extractors, the con-

veyors, the shaking and norias in washing

position. Operate the machine for 2 to 3 min-

utes to allow the water to drain off.

After cleaning has been completed, the machine

will be ready for daily lubrication.

NOTE: after greasing, remember to reposition the

inspection doors, the plates, etc... which were

opened during the washing operations.

604 82 321 00 -02 - 2005


12 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 13

HYDROSTATIC AND HYDRAULIC SYSTEM MAINTENANCE

1) Intake and return filter cartridge replace-

ment

This cartridge must be replaced:

a) every 800 hours,

b) or every two years,

c) at each discharging.

2) Draining and refilling the circuit

Drain the circuit every 800 hours and at least every

two campaigns.

Always observe the following recommendations:

a) fill the oil reservoir completely with the recom-

mended oil immediately at the end of the cam-

paign, to prevent condensate from forming be-

tween two seasons.

The oil must be filled by means of a pump

through the quick return coupling, so as to filter

the oil, or through the suitable fitting.

b) Before the following campaign and, compulsor-

ily, before starting the thermal engine, empty

the tank partially to ensure a perfect oil settling.

c) Check the oil level in the reservoir.

IMPORTANT: when topping oil up, use the same

type used for the initial filling.

When draining oil, work with great care and cleanli-

ness. Clean by a jet of compressed air or a clean

brush and oil the drain and filling holes before disas-

sembling them, so that no foreign impurities or

matters enter the circuit.

Remove the drain nut under the reservoir. Empty the

reservoir only.

During drain operations, replace the cartridges of the

intake filter and of the return filter.

604 82 321 00 -02 - 2005


14 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


ROUTINE MAINTENANCE

Engine

SECTION 00 - MAINTENANCE - CHAPTER 1 15

-- Oil change every 400 hours or once a year

(incaseofACEAE3orE5oil).

-- Oil and fuel filter change every 400 hours

or once a year.

-- Belt tension adjustment every 400 hours or

onceayear.

-- Level check and cleaning of the radiator

core every day, or every 10 hours.

-- Tappet adjustment every 1200 hours (see

section 10).

-- Injector calibration adjustment every 1200

hours (see section 10).

IMMEDIATELY AFTER EACH CAMPAIGN

Disassemble:

-- the shakers without the link rods

-- the right and left bucket chains

-- the conveyor belts.

Carefully clean the above assemblies.

Repair broken buckets and removed small blocks.

in a ventilated room, protected against ro-

Store

dents:

the bucket chains, which should be ex-

--

to prevent bucket deformation.

tended

the conveyor belts, which should be laid

--

transversely.

out

-- the shakers, which should be laid out flat.

Carefully clean the rail assembly and the conveyor

bodies, using a water jet. Drain the inside water.

Check that no harvest residue remains in the ma-

chine.

WINTER STORAGE

Hydraulic system

-- Oil change every 800 hours or every 2

years.

-- Oil filter change every 800 hours or every

two years.

-- Protection sleeve condition control.

-- Detection and repair of possible leaks.

-- Priming and exchange pressure control.

Mechanical system

Wheel tightening check (see section 44)

every 50 hours and then every 400 hours.

Steering limiter adjustment check (see sec-

tion 41) every 50 hours and then every 1200

hours.

AFTER WASHING

for wear on the inner side of the rails and

Check

slides.

the machine assembly (self--propelled ma-

Grease

+ harvesting machine).

chine

the harvesting devices (shaking, con-

Operate

etc...) for half an hour.

veyor,

all the grease fittings on the harvesting ma-

Refill

(shaker link rods, shaking system controls,

chine

front plate and bottom roller greasers).

Replace the worn or damaged parts.

the machine (or just the harvesting machine)

Store

a covered, closed and dry area.

in

the machine on blocks to relieve the tyres,

Support

whichshouldbeleftinflated.

up the paintwork as necessary and replace

Touch

defaced safety decals.

any

the operation of the steering valve (push

Check

return).

button

Retract all cylinders and grease all unpainted

mechanical parts (shafts, pins, adjustment rods,

cylinder rod outlet ends, rails, slides, antiskid valve

push button, etc...).

604 82 321 00 -02 - 2005


16 SECTION 00 - MAINTENANCE - CHAPTER 1

Self -propelled machine not used as multi -

function

Completely fill the fuel tank and the hydraulic res-

ervoir to prevent condensation.

Make sure the concentration of antifreeze in the

cooler is sufficient for local temperature conditions.

Change the thermal engine oil and the oil filters.

Bleed the fuel filters.

Seal the intake and exhaust ports, making them

tight.

Detach the battery, clean and recharge it. Grease

the terminals with acid--proof grease.

604 82 321 00 -02- 2005

ONCE A MONTH:

-- remove a small amount of oil from the hydraulic

reservoir.

-- Remove the intake and exhaust port guards.

-- Assemble the battery again.

-- Operate the engine on road and let it run for the

time required to reach a temperature by about °.

-- Operate all the machine parts (extractors, con-

veyors, lifting, steering, ...).

-- Operate the cab air conditioning system.

-- Stop the engine.

-- Top up the hydraulic reservoir.

-- Remove the battery.

-- Refit the intake and exhaust port guards.


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 1

SECTION 05 - MACHINE PREPARATION AND EQUIPMENT

Chapter 1

CONTENT

Description Page

......................................................

Section

adjustment 2

...........................................................

Console

604 82 321 00 -02 - 2005


2 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005

22 mm

B

7�

A

45 mm


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 3

INCHING CONSOLE

1) This console can be adjusted forwards and backwards by 45 mm. To this purpose, loosen the two lock--

nuts (A) and the screw located inside the housing.

2) The inching lever can be adjusted as for its height -- 22 mm -- and its sloping is adjustable by 7�; tothis

purpose, loosen the three screws (B).

CHECKS

Check all levels:

-- engine oil

-- hydraulic oil

-- coolant

-- windscreen washer fluid

Check all the machine functions.

SHAKER ASSEMBLY

After analyzing the vineyard structure, assemble the shakers following the instructions of section 58.

604 82 321 00 -02 - 2005


4 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 10 - ENGINE - CHAPTER 1 1

SECTION 10 - ENGINE

Chapter 1 - Engine

CONTENT

Operation Description Page

specifications 2

.........................................................

General

5

.........................................................................

Data

torques 15

...........................................................

Tightening

17

.......................................................................

Tools

views 18

................................................................

Engine

diagram 20

..........................................................

Lubrication

diagram 22

.............................................................

Cooling

diagnosis 26

..............................................................

Fault

001 30 Engine. Compression Test 30

.....................................................

10

001 53 Engine D.A. Checks, measurements and repairs 31

.................................

10

102 70 Crankshaft front seal -- Replacement 94

...........................................

10

102 74 Crankshaft rear seal -- Replacement 96

............................................

10

106 12 Valve tappet and rocker arm clearance -- Adjustment 100

.............................

10

218 30 Engine injector R.I. 101

..........................................................

10

246 14 Bosch injection pump R.I. Timing. Air bleed 102

.....................................

10

402 10 Coolant pump R.I. 110

...........................................................

10

402 30 Thermostat valve R.I. 112

........................................................

10

414 10 Coolant pump and generator drive belt. Tension adjustment 113

.......................

10

604.82.321.00 -02 - 2005


2 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Engine, technical type:

model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601

--

pump)

(BOSCH

604.82.321.00 -02- 2005

Seedataonpage6

-- model VL610 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL620 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL630 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL640 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL660 -- type F4GE0684C*D600 (BOSCH pump) Seedataonpage9

Cycle ............................................... diesel, 4--stroke

Fuelinjection ........................................

Direct

Numberofcylindersinline............................. 4 6

Piston diameter

mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620 -- VL630

--

................................. 4.094 in. (104 mm)

--VL640--VL660

Pistonstroke ........................................ 5.197 in. (132 mm)

Total displacement:

-- modelVM460--VM370--VL570 .................... 4485 cm 3

-- mod.VL610--VL620--VL630--VL640--VL660 ...... 6728 cm 3

ratio for Mod. VM460 -- VM370 -- VL570 --

Compression

VL620--VL630--VL640--VL660 .............. 17,5:1

VL610--

Maximum power:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 94 kW (128 HP)

-- modelVL610--typeF4GE0684G*D600 .............. 107 kW (145 HP)

-- modelVL620--typeF4GE0684G*D600 .............. 107 kW (145 HP)

-- modelVL630--typeF4GE0684E*D600 .............. 120 kW (160 HP)

-- modelVL640--typeF4GE0684E*D600 .............. 120 kW (160 HP)

-- modelVL660--typeF4GE0684C*D600 .............. 129 kW (175 HP)

Maximumpowerspeed ............................... 2300 rpm

Maximum torque: model VM460 -- VM370 -- VL570 -- type

--

F4GE0484C*D601

500 (Nm)

-- Maximum torque: model VL610 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL620 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL630 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL640 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL660 -- type F4GE0684C*D600 700 (Nm)

Maximumtorquespeed ............................... 1400 rev/min

Numberofmainbearings .............................. 5 7

Sump ............................................... steel

(continued)


SECTION 10 - ENGINE - CHAPTER 1 3

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Lubrication ........................................... forced, with gear pump

Pumpdrive ............................................ camshaft

Enginespeed/oilpumpspeedratio ....................... 2:1

with mesh filter on oil intake and cartridge

Oilfiltering.............................................

on delivery line

filter

Normal oil pressure with motor warmed--up

atslowidling........................................... 10.15 psi (0.70 bar)

atfastidling ........................................... 50.76 psi (3.50 bar)

Cooling .............................................. coolant circulation

on mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620

Radiator

VL630--VL640--VL660 ............................... Engine coolant and hydraulic circuit fluid

--

Fan,drivenbyahydraulicmotor.......................... suction, steel with 8 blades

Coolantpump..........................................

Coolantthermometer ...................................

Temperature ranges corresponding to each section:

-- greensector(normalconditionsofuse) ..................

-- redsector ...........................................

At 221 °F (105°C) every minute

Caution!

230 °F (110°C) every 10 seconds

under

centrifugal vane--type

with 12 segments

104 °F --212°F (40°C --100°C)

212 °F --248°F (100°C --120°C)

Enginespeed/coolantpumpspeedratio ................... 1:1,977

Temperaturecontrol .................................... via thermostat valve

-- initialopening....................................... 177.8 ± 35.6 °F (81± 2 °C)

system ........................................ overhead valves operated by tappets, rods

Timing

rocker arms via the camshaft located

and

Intake:

(cont)

the engine block; the camshaft is driven

in

the crankshaft using straight--tooth

by

gears

-- start:beforeT.D.C. .................................. 15°

-- end:afterB.D.C. .................................... 35°

Exhaust:

-- start:beforeB.D.C. ................................. 69°

-- end:afterT.D.C. .................................... 21°

Clearance between valves and rocker arms with engine cold:

-- intake ............................................. 0.009 ± 0.001 in. (0.25 ± 0.05 mm)

-- exhaust ............................................ 0.019 ± 0.001 in. (0.50 ± 0.05 mm)

For further timing system technical data ................... see page 12

(continued)

604.82.321.00 -02 - 2005


4 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Fuel system

with dual cartridge dry air filter, with

Airfiltering.............................................

filter indicator

clogged

Fuelpump............................................. with double diaphragm

........................................... through wire filter in fuel supply pump, and

Fuelfiltering

cartridge on delivery line to

replaceable

604.82.321.00 -02- 2005

injection pump

Camoperated ......................................... engine timing

BOSCHinjectionpump.................................. rotating distributor type

All--speed governor, incorporated in pump:

BOSCH ............................................... centrifugal counterweights

Automatic advance regulator, incorporated in pump:

BOSCH ............................................... hydraulic

For further fuel system technical data:

advance (pump setting for start of delivery before TDC)

Fixed

Pressure setting -- Injection order, and other information

--

............................. refer to the data for the relevant engine

regardingtheBOSCHpump

in the table on page 2

type

(cont)


Turbocharger:

SECTION 10 - ENGINE - CHAPTER 1 5

FUEL SYSTEM DATA

For version F4GE0484C*D601:

--

.............................. GKB13L/A085BXL

--typeHOLSETHX27W

For versions F4GE0684C*D600 -- F4GE0684E*D600 --

--

F4GE0684G*D600:

--typeHOLSETHX35W ..............................

E7735AG/E16XB11

......................................... rotating distributor with speed governor

Injectionpump

advance regulator incorporated

and

BOSCH pump:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 VE 4/12 F 1150 L 956 -- 504053467

-- modelVL610--typeF4GE0684G*D600 ................ VE 6/12 F 1150 L 964 -- 504060083

-- modelVL620--typeF4GE0684G*D600 ................ VE 6/12 F 1150 L 964 -- 504060083

-- modelVL630--typeF4GE0684E*D600 ................ VE 6/12 F 1150 L 981 -- 504060084

-- modelVL640--typeF4GE0684E*D600 ................ VE 6/12 F 1150 L 981 -- 504060084

-- modelVL660--typeF4GE0684C*D600 ................ VE 6/12 F 1150 L 978 -- 504053466

Directionofrotation ..................................... anticlockwise

.........................................

Injectionorder

modelVM460--VM370--VL570 ...................... 1--3--4--2

--

-- mod.VL610--VL620--VL630--VL640--VL660 ........ 1--5--3--6--2--4

Fuel injectors:

BOSCHtype.............................

VM460

VM370

VL570

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 . 504063465

F4GE0684E*D600

DSLA

P 1174

145

VL610

VL620

504063465

DSLA

145 P 1174

VL630

VL640

504063465

DSLA

145 P 1174

VL660

504063465

DSLA

145 P 1174

Numberofnozzleholes ................... 6 6 6 6

Nozzleholediameterin.(mm.) .............

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 .

F4GE0684E*D600

0.009

(0.223)

.............. 3771 to

Calibrationpressurepsi(bar)

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

604.82.321.00 -02 - 2005


6 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VM460 - VM370 - VL570 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 4/12 F 1150 L 956

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1150 0.091 -0.138

1.1

-3.5) (2.3

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1.../2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 73.5 -79.5 cc/1000 0

Difference

cc/1000

700 103.5 -109.5 cc/1000 1000 3.5

1.4 Minimum 400 6.5--18.5 cc/1000 0 6.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1280 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(11.0--21.0) - (0 .3 -- 0.5 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1150

0.091--0.138 (2.3--3.5)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1280 max. 3.0 1000

p p p

Lever

-

-

1150 95.0--101.0 1000

700 103.5 -109.5 1000

700 88.0 -94.0 500

500 73.5 -79.5 0

Minimum 400 6.5--18.5 0

450 max. 3.0 0

curve 100 > 80.0 0

g Starting

300 < 93.5 0

-

-

-

--

--

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

-


SECTION 10 - ENGINE - CHAPTER 1 7

VL610 - VL620 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 6/12 F 1150 L 964

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1000 0.063--0.110

1.1

-2.8) (1.6

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1.../2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 86.2 -92.2 cc/1000 0

Difference

cc/1000

700 80.8 -86.8 cc/1000 1000 3.5

1.4 Minimum 360 7.0--23.0 cc/1000 0 5.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1290 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(6.0--16.0) - (0 .4 -- 0.6 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1000

0.063--0.11 (1.6--2.8)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1290 max. 3.0 1000

p p p

Lever

-

-

1150 75.0 -81.0 1000

900 80.8 -86.8 1000

500 92.5 -98.5 325

500 86.2 -92.2 0

Minimum 360 7.0--23.0 0

420 max. 3.0 0

curve 100 > 80.0 0

g Starting

250 < 107.0 0

-

-

-

1150

2.1--3.3

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

604.82.321.00 -02 - 2005

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8 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VL630 - VL640 - CALIBRATION DATA

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Источник: [https://torrent-igruha.org/3551-portal.html]

MONDAY, OCTOBER 20, 2014   9:00-17:00

POSTER PLUS VIDEO I – Poster Exhibition – Hall XL__________

P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN; COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY

N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1, S. Date1, J. Bapaye3

1Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale Medical College, Pune, India

Contact E-mail Address:[email protected]

INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis. The best approach for drainage of these collections is still controversial. We present our retrospective data comparing the two endoscopic methods for drainage of WOPN.

AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural drainage (EUTMD) using a newly designed fully covered large-bore wide-flare metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who underwent placement of multiple plastic stents (Gr II). The pre-op CECT confirmed suitability of endoscopic drainage based on location, wall thickness & contents. Visual quantification of necrosis (>50% solid debris) by EUS excluded 8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by standard technique by a single endoscopist. The difference between the two groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of NCT and subsequent necrosectomy was done whenever necessary. Follow-up imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes were compared in terms of clinical success, need for surgery, complications, hospital stay and mortality.

RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of demographics, etiology of pancreatitis, cyst location, size and amount of debris. Placement of NCT, need of necrosectomy and no of sessions required were also not different between the two groups. Clinical success defined as resolution of symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p = 0.048). None of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II (p = 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p = 0.016)

Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p = 0.012). Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p = 0.22)

CONCLUSION: The Nagi stent™ is effective and safe for EUTMD of WOPN. It permits rapid clinical resolution with 100% technical and clinical success rates. It offers distinct advantage over plastic stents although further prospective studies are warranted.

Disclosure of Interest: None declared

P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF THE ESOPHAGUS USING A “RENDEZ-VOUS” TECHNIQUE

J.-M. Gonzalez1,*, G. Vanbiervliet2, M. Barthet1

1Gastroenterology, Aix-Marseille University, North Hospital, Marseille, 2Gastroenterology, Nice Hospital, Nice, France

INTRODUCTION: Complete esophageal obstruction leads to definitive fasting. The rendez-vous endoscopic approach had already been described for complex stenoses as an alternative to surgery that has high morbid-mortality.

AIMS & METHODS: This is a case series report about six patients referred for complete esophageal disruption classified in two groups: 1/ Long disruption (> 5cm), one after caustic ingestion and two due to an esophageal stripping during SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (< 5cm), consecutive to radiation therapy for a neck neoplasia. They had been fasting for 3 to 18 months. All the procedures were performed according the anterograde retrograde approach, under anesthesia and with CO2 insufflation and X-rays guidance.

RESULTS: There were 3 men and women between 25 and 71 years old. All the reconstructions have been successful in one to three endoscopic sessions, using the non hydrophilic tip of a guide wire passed through a straight catheter in 5 cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created, by transillumination (n = 1) or head and neck surgery (n = 1). In order to guide the reconstruction, SEMS was used in one case, NGT in one case, and both were used in one patient. The first dilation was performed with a CRE balloon (12-15mm). All the patients could eat mixed after 2 POD. There was no intra-operative or post-operative complication. Then, the patients underwent 3 to 18 dilations sessions during 1.5 to 15 months; two are still undergoing dilations and all eat normally.

CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe and effective in case of esophageal disruption even with loss of SES, avoiding surgery.

Disclosure of Interest: None declared

P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY GASTRIC CANCERS USING THE CLUTCH CUTTER

K. Akahoshi1,*, Y. Motomura1, M. Kubokawa1, J. Gibo1, N. Kinoshita1, S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1, N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1

1Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: To reduce the risk of complications related to ESD using conventional knives, we developed the Clutch Cutter (CC), which can grasp and incise the targeted tissue using electrosurgical current.

AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients (228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intramucosal or superficial submucosal gastric cancer without lymph node involvement, that had been confirmed by preliminary endoscopy, EUS, and endoscopic biopsies, were enrolled into this prospective study. The CC was used for all steps of ESD (marking, circumferential marginal incision, submucosal dissection, and hemostatic treatment). The therapeutic efficacy and safety were assessed.

RESULTS: The mean size of the early gastric cancers and resected specimens was 17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes. The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respectively. The R0 resection rates according to tumor size and location were 97.4% (229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9% (127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/95) in upper portion. The mean operating time according to tumor size and location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9 min in lower portion, 108.8 min in middle portion, and 117.2 min in upper portion. Perforation during ESD occurred in one case (0.3%), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully treated by endoscopic hemostatic treatment.

CONCLUSION: ESD using CC is a safe and technically efficient method for resecting early gastric cancers.

REFERENCES

1) Akahoshi K, Akahane H, Murata A, et al. Endoscopic submucosal dissection using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.

2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic submucosal dissection using the clutch cutter for early stage digestive tract tumors. Digestion 2012: 85: 80-84.

Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM have applied for the patent in Japan, Europe, and USA for the Clutch Cutter described in this article. China has already granted the patent., Y. Motomura: None declared, M. Kubokawa: None declared, J. Gibo: None declared, N. Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T. Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya: None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M. Oya: None declared

P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS

M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T. Ponchon5

1Gastroenterology and endoscopy, Hôpital Edouard Herriot, 2Inserm U1032, 3Functional disorders unit, Hôpital Edouard Herriot, Lyon, France, 4Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania, 5Gastroenterology and endoscopy unit, Hôpital Edouard Herriot, Lyon, France

Contact E-mail Address:[email protected]pueihtam

INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising method for the treatment of the esophageal achalasia. But the precise technique can be refined. We developed a combined technique of water jet system for tunnelling and hook knife section for myotomy and we evaluated its results in a prospective study.

AIMS & METHODS: The patients presented with an achalasia without any prior instrumental treatment. The submucosal tunnel was created 12 cm over the cardia and 3 cm below, and then the endoscopic myotomy was performed using the Olympus Hook Knife by a single operator with CO2 insufflation, beginning 8 cms over the cardia and finishing 2 cms below. The clinical evaluation was realized before and then after the procedure at 1, 3, 6 and 12 months (score of Eckardt, score of quality of life GIQLI). A high-resolution manometry was realized before POEM and 3 months later to classify the achalasia (classification of Chicago) and to measure basal pressure and pressure of relaxation integrated (PRI) of the lower esophageal sphincter. Then an esophageal pHmetry of 24 hours was performed at 3 months to diagnose GERD. The data are expressed in median (extremes) and compared before and later myotomie by paired t-test.

RESULTS: 21 patients (13 men, average age 61 years) were included. 18 procedures were complete, 1 was not realized because of a large esophageal diverticulum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries occurred but did not prevent to continue the procedure after mucosal closure by clips. Dual Knife ® (n = 7) or the water jet Nestis Enki 2 ® (n = 11) were used for the tunnel. No mucosal injuries were observed with the water-jet system. Hook Knife ® was used for all myotomies. The average time of procedure was 94.2 min with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated with a needle during the procedure in 13 cases without any visible perforation. CT scan at day 1 showed a pneumomediastinum (n = 14/18), a pneumoperitoneum (n = 14/18) and/or a peumothorax (n = 3/18). No sepsis was observed. Feeding was always possible with liquids at day 1. All patients noted a clinical improvement. At 3 months, the basal pressure of the SIO was decreased for all patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p<0.01) as well as the PRI (8 mmHg (0-16) against 23 mmHg (9-28), p<0.01). pH metry showed a pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases.

Inclusion1 month3 months6 months1 year
n211714103
Eckardt6 (3-11)1 (0-3)*1 (0-3)*0 (1-4)*0 (0-0)*
GIQLI82 (50-114)115 (66-135)*115 (82-140)*131 (94-143)*140 (130-142)¥

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CONCLUSION: Water-jet injection allows rapid and safe tunneling of the submucosa and myotomy with hook knife is very precise. Safety and effectiveness of mytomy is reinforced using these technical refinements.

Disclosure of Interest: None declared

P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGH-MAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY FOR DIFFERENTIATION OF GASTRIC LESIONS

R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3, E. Nikonov4, V. Kapranov5, A. Rusakov6

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation, 2Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G. Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic №1 of the Business Administration for the President of Russian Federation, Moscow, 5Internet Center, 6Administration, P. G. Demidov Yaroslavl State University, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: High-magnification endoscopy with narrow-band imaging (HME-NBI) has been used for diagnosis of gastric pathology because of its high accuracy. Nevertheless, the application of these advanced techniques in clinical practice is difficult due to the presence of various histological changes of gastric mucosa with different modifications of microvascular and microsurface patterns. Newly developed computer-aided decision support systems are designed to detect and/or classify abnormalities and thus assist a medical expert in improving the accuracy of medical diagnosis. However, there is lack of data for computer-aided devices for classification of gastric lesions with HME-NBI.

AIMS & METHODS: The aim of this study was to evaluate the effectiveness of computer-aided classifier of endoscopic magnification images of gastric lesions. We analyzed our database contains 78 endoscopy NBI magnification images of gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images were classified into three classes: oval (13 images), tubular (31 images), and destroyed with vessel network (34 images). Initially we divided images of every class into two sets — training set and test set. Then we selected uniformly distributed random points with fixed density (one random point for every 300 pixels) at every picture, which were analyzed by extracting topological features for building the classifier. Training set images were used for classifier training with Adaboost algorithm and testing set images of each group were utilized for testing with previously trained classifier. We repeated the procedure described above for the estimation of classifier quality.

RESULTS: From 78 database images there were 50 images (66.6%) with the success rate of correct classification exceeding 80%. In 14 images (17.9%) all points (100%) were recognized correctly. The mean percentage of points with the correct classification was 79%.

CONCLUSION: Topological features were successfully used for description of endoscopic magnification images. The combination of topological features analyzed with Adaboost algorithm allowed for creating and effective training of computer-aided classifier of endoscopic magnification images of gastric lesions.

Disclosure of Interest: None declared

P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS CONDITIONS AND LESIONS OF THE STOMACH

R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration, Polyclinic №1 of the Business Administration for the President of the Russian Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: Endoscopic mapping of the entire stomach with advanced techniques has been recommended as an important step of surveillance of premalignant gastric conditions/lesions [1]. Although current imaging technologies, such as narrow-band imaging (NBI) and high-magnification endoscopy, allow enhanced visualization of gastric mucosa, their application is still limited due to low contrast and brightness of endoscopic view and complexity of usage. Newly developed NBI system with dual focus (DF) magnification might be a promising tool to overcome this challenge.

AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy of new NBI-DF system in detection, characterization of gastric lesions in patients with extensive atrophy and/or intestinal metaplasia. A total of 43 patients (mean age 51.3 years, SD = 12.1) were initially examined by conventional white light endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy (CE) with indigocarmine was performed as the “gold standard” for detection of lesions. Any suspicious areas detected by NBI or CE were subsequently further assessed with NBI with DF (Olympus Exera III GIF H190) and characterized accordingly. Biopsies were taken from all lesions for histological assessment.

RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic (chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 high-grade dysplasia/early gastric cancer. All lesions (100%) detected by CE were found with NBI observation. Endoscopic histology prediction was successful in 88 cases (94.6%) Endoscopic misdiagnosis was found in 5 cases (5.4%): overestimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive predictive value and negative predictive value were 80%, 97.4%, 85.7% and 96.2% respectively for early gastric cancer/high-grade dysplasia.

CONCLUSION: Observation of gastric mucosa with a novel NBI system was at least as effective as CE with indigocarmine in detection of suspicious gastric lesions in patients with precancerous conditions and lesions of the stomach. Dual focus magnification provides sufficient assessment of microvascular and microsurface patterns in order to differentiate gastric lesions. Further randomized controlled studies are needed to be performed for clarifying the role of novel endoscopic system in diagnosis of gastric pathology.

REFERENCES

1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.

Disclosure of Interest: None declared

P0007 DEVELOPMENT OF A PROTOTYPE OF VIDEO SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES DURING ENDOSCOPIC EVALUATION OF BARRETT’S OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL STUDY

S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1

1CHU Strasbourg, 2IRCAD, Strasbourg, France

Contact E-mail Address:[email protected]

INTRODUCTION: The prevalence of Barrett's oesophagus (BE) is 5 to 6% in the general population, with a progression from dysplasia to adenocarcinoma 0.6 to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early lesions accessible to endoscopic treatment. However, the relocalisation of lesions detected by biopsies may be difficult during follow-up endoscopies. The purpose of this study was to evaluate the prototype of a magnetic probe for accurate location of the position of the endoscope, allowing the relocalisation of this position in a subsequent endoscopy. We report the results of a feasibility study in pigs and the use of this device in two patients with BE.

AIMS & METHODS: The system consists of an electromagnetic (EM) field transmitter and an EM probe constituting the electromagnetic tracking system (EMS) (NDI, Aurora). The EM probe is inserted through the operating channel of a double channel gastroscope. The EM field generator is positioned on the patient's chest wall. The system also includes new software developed at IHU/IRCAD, which performs simultaneous recording of the video from the endoscope alongwith its corresponding position, as measured by the EMS. During a second endoscopy, this software allows automatic synchronisation of the recorded video to provide relocalisation of the endoscope in front of previous biopsy sites in the oesophagus.

The system was tested in 5 anesthetised pigs. During the first endoscopy, ten markings were performed by argon plasma electrocoagulation (ERBE Tübingen, Germany) in the distal oesophagus. The position of each marking was recorded by the system. A second operator to then performed a blind endoscopy on the same pigs and was asked to follow the system implicitly as a guide to relocate the markings.

In 2 patients with BE, the system was then tested to facilitate relocalisation of the biopsy sites.

RESULTS: Ten markings were made in the distal oeosphagus of 5. After withdrawal of the endoscope the second operator found 48 of the 50 markings (96%) using the guidance provided by the system. The positioning of the endoscope provided by the EMS system was within a 2mm range from the initial positionning. In the evaluation of BE patients, the system relocalised the biospy sites within a range of 3mm.

CONCLUSION: This preliminary study shows the feasibility of the EMS prototype to relocalise the endoscope in the oesophagus within an acceptable range. The clinical usefulness of this system should be evaluated further during the follow-up of patients with BE.

Disclosure of Interest: None declared

P0008 THE UTILITY OF ROUTINE CHROMOENDOSCOPY FOR DETECTION OF DYSPLASTIC LESIONS DURING SURVEILLANCE COLONOSCOPY IN PATIENTS WITH COLONIC INFLAMMATORY BOWEL DISEASE. DOES RESEARCH TRANSLATE TO CLINICAL PRACTICE?

U. Javaid1, R. Thethi1, P. Luthra1, N. Mohammed2,*, J. Hamlin1, B. Rembacken1, V. Subramanian2

1Gastroenterology, St James University Hospital, Leeds Teaching Hospital NHS Trust, 2Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective studies to improve dysplasia detection rates by improving the ability to detect subtle mucosal changes. (1) The utility of CE in dysplasia detection in patients with IBD during routine clinical practice has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by CE with standard white light endoscopy (WLE).

AIMS & METHODS: Retrospective cohort study of patients with long standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching Hospital NHS Trust between January 2012 to December 2013. Details of diagnosis, duration of disease and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records and patient notes.

RESULTS: There were 120 colonoscopies in the CE group and 220 colonoscopies in the WLE group. The groups were well matched for all demographic variables. 27 dysplastic lesions were detected in 20 patients in the CE group and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the lesions were detected on targeted biopsy and harboured low grade dysplasia. The adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic lesion was 4.6 (95% CI 1.6-13.7) in favour of CE.

CONCLUSION: CE colonoscopy improves detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD even in routine clinical practice, confirming data from prospective trials. CE should be the standard of care for all IBD surveillance procedures as advocated by both BSG and ECCO guidelines.

REFERENCES

(1) Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 304-312.

Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014   9:00-17:00

LIVER & BILIARY I – Poster Exhibition – Hall XL__________

P0009 INVOLVEMENT OF B-CELLS IN HEPATIC INFLAMMATION DURING NONALCOHOLIC STEATO-HEPATITIS (NASH)

A. Jindal1,*, S. Sutti1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1 on behalf of Laboratory of General Pathology, Prof. Albano, Novara, Italy

1Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Growing evidence indicates that adaptive immunity contributes to the process leading to chronic hepatic inflammation in NASH. However, the mechanisms involved are still incompletely characterized. Recently, B-lymphocytes have emerged as players in orchestrating adipose tissue inflammation in obesity contributing to the development of insulin resistance.

AIMS & METHODS: We investigated the possible role of B-cell responses in the pathogenesis of NASH. NASH was induced by feeding four weeks C57BL/6 mice with a methionine-choline deficient (MCD) diet.

RESULTS: In mice receiving the MCD diet the development of steatohepatitis was associated with an increased hepatic infiltration by B220 (CD20) positive B-lymphocytes and by the detection of circulating IgG targeting oxidative stress-derived antigens such as malonildialdehyde- (MDA) and 4-hydroxynonenal-protein adducts. Moreover, immunohistochemistry showed the presence of IgG deposits within the hepatic inflammatory infiltrates that co-localized with MDA-derived antigens, indicating the formation of immunocomplexes. To substantiate the role of oxidative stress in triggering B-cell responses in NASH, mice were immunized with MDA-adducted bovine serum albumin (MDA-BSA) before feeding the MCD diet. In MCD-fed, but not in control mice, MDA-BSA immunization promoted liver B-cell expansion and enhanced transaminase release, lobular inflammation and the hepatic production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-12. Among immunized MCD-fed mice there were also positive correlations between the individual expression of the B-cell marker B220 and those of macrophage M1 activation markers IL-12p40 and iNOS (r = 0.87 and 0.71 respectively; p<0.02).

This effect was likely mediated by B-cell interaction with CD4 T-cells as in the same animals B220 expression also positively correlated with that of IFN-γ (r = 0.76; p<0.03) and of the co-stimulatory molecule CD40 (r = 0.72; p<0.05). Furthermore, depleting CD4+ T-cells in MCD-fed immunized mice by using an anti-CD4 monoclonal IgG did not affected B220 expression, but significantly lowered the hepatic mRNAs IFN-γ, iNOS and IL-12p40 and ameliorated lobular inflammation and focal necrosis.

CONCLUSION: These results indicate that B-cell responses triggered by oxidative stress can contribute to inflammation in NASH by stimulating T-cellular responses.

Disclosure of Interest: None declared

P0010 GENERATION OF A VECTOR CONTAINING AN SHRNA FOR THE RECEPTOR CB1 AS AN ANTIFIBROGENIC STRATEGY IN LIVER DISEASE

A. Díaz Rivera1,*, V. Chagoya de Sánchez 2, G. Velasco Loyden 2, L. García Benavides 3, J. Armendáriz Borunda 1, A. Sandoval Rodríguez1

1Molecular Biology and Gene Therapy Institute, Guadalajara, 2Cellular Physiology Institute, México, D. F, 3Institute of Experimental and Clinical Therapeutics, Guadalajara, Mexico

Contact E-mail Address:[email protected]

INTRODUCTION: Blockade of cannabinoid type I receptor (CB1) by pharmacological antagonist has demonstrated antifibrogenic effects in models of cirrhosis. Gene therapy with a shRNA molecule for CB1 wthinin an adenovirus has the advantage of hepatic tropism, which will reduce side effects and increase the transduction efficiency.

AIMS & METHODS: Design a shRNA that efficiently inhibit the expression of CB1, evaluate its antifibrogenic effect in an experimental model of liver cirrhosis and generate an adenoviral vector coding for the shRNA-CB1.

shRNA sequences were designed to blockade mRNA of CB1 at positions 877, 1232, 1501 (pshCB1-A, B, D). The effectiveness of the shRNA was evaluated by inhibition of the mRNA-CB1 after transfection of the plasmids in primary culture rHSC. To determine the optimum dose for transfection in primary cultures, lipofectamine 2000 and Fugene ® HD were tested using a GFP expressing plasmid (pITR-GFP). Later, we evaluated shRNA mediated-CB1 inhibition in cirrhotic rats intoxicated with CCl4. The plasmids were administrated by hydrodynamic injection in a volume of 4 mL. Then, in animals transfected with the most potent shRNA-CB1, mRNA levels of fibrogenic molecules (TGF-β1, Col 1 and α-SMA) and percentage of fibrotic liver tissue was measured. Finally, Ad5 backbone coding for shRNACB1-1232 or shRNA-Irrelevant was generated by homologous recombination between pshRNA and the pAd / BLOCK-iT ™ DEST.

RESULTS: In vitro shRNA designed to block position 877 and 1232 significantly inhibited mRNA (p> 0.05) CB1 gene expression in 77% and 91%, respectively using Fugene ® HD. The sequence of shRNA-Irrelevant did not affect mRNA expression of CB1. Hydrodynamics-based transfection of shRNA-CB1 via iliac vein in the rat allows efficient and repeatable delivery to the liver. A volume of 4 mL carrying 3 mg/kg was administered in 5-7 seconds. In CCl4 model shCB1-1232 showed major decrease in CB1 mRNA and protein (p<0.05), and in consequence fibrogenic molecules TGF-β1, Col I, α-SMA also reduced (60%, 47% and 77% (p<0.05); respectively). Fibrosis diminished 49% (p<0.05) compared to untreated controls. Thus pshRNACB1-1232 was selected for production of adenovector. Homologous recombination between attL and attR regions between pshRNA-1232-CB1 and pAd / BLOCK-iT ™ DEST allowed the generation of Ad-shRNA1232-CB1 backbone.

CONCLUSION: shCB1-1232 demonstrates CB1 gene and protein silencing in vitro and in vivo, decreasing mRNA levels of key fibrogenic molecules and fibrosis, showing potential to be used as therapeutic strategy for liver fibrosis. Recombinant adenovirus expressing this shRNA will have the advantage of high titers production conserving efficient liver transduction, which will facilitate its therapeutic application in experimental models of liver cirrhosis or even clinical scenarios.

Disclosure of Interest: None declared

P0011 CORRELATION BETWEEN INDIRECT SERUM MARKERS AND MORPHOMETRIC VALUES OF FIBROTIC TISSUE IN PBC

C. Stasi1,*, L. Leoncini1, M.R. Biagini1, S. Madiai1, F. Marra1, G. Laffi1, S. Milani2

1Department of Experimental and Clinical Medicine, 2Department of Biomedical, Experimental and Clinical sciences, University of Florence, Florence, Italy

INTRODUCTION: The accuracy of non-invasive methods for the quantification of liver fibrosis in patients with PBC is still debated. Moreover, the Ludwig’s PBC stages do not represent a measurement of quantitative fibrosis.

AIMS & METHODS: We determined the histomorphometrical measurement of fibrotic tissue and analyzed the accuracy of a number of indirect markers of liver fibrosis for the detection of different histological stages of PBC and the association between indirect serum markers and morphometric values (MV) of fibrotic tissue.

Methods: Sections of liver tissue were stained with hematoxylin/eosin and

Sirius red. Only samples with a > 25 mm length and including at least 11 complete portal tracts were considered adequate for the study. Histomorphometrical measurement of fibrotic tissue was performed on sirius red stained sections of liver biopsies. Area percentage measures of fibrotic tissue were ranked into 4 groups reflecting Ludwig’s staging and compared with values of the following serum markers of liver fibrosis: APRI, LOK, FORNS, FIB-4. The percentage of fibrosis was calculated with ImageJ. All results were expressed as mean ± standard deviation. The numerical comparison of continuous data was performed using the Wilcoxon signed ranks test applied to two-samples. Linear regression analysis between two variables was performed by using Pearson correlation. Statistical significance was set at a value of p<0.05.

RESULTS: We enrolled 50 patients with PBC (mean age, 57±12.30 years; 43 F and 7 M; 8 AMA negative, 42 AMA positive). There were 19 (38%) patients in Ludwig’s PBC stage I, 14 (28%) in stage II, 12 (24%) in stage III and 5 (10%) in stage IV. The morphometric values (Table 1) of fibrotic tissue were significantly different in the various Ludwig’s stages of PBC (p<0.05). Only LOK score was statistically different between stage II and III (p = 0.02). No other significant differences were found in the various Ludwig’s stages of PBC for APRI, FORNS, FIB-4 and LOK scores (Table 1). A statistically significant correlation was found between MV and Forns (R2 = 0.3643, p = 0.0004), MV and FIB-4 (R2 = 0.3945, p = 0.0002), MV and LOK (R2 = 0.3367, p = 0.0010), MV and APRI (R2 = 0.1476, p = 0.0361).

Table 1.

Ludwig's stagesMorphometric valuesFORNSFIB-4LOKAPRI
Stage I0.74% ± 0.653.61 ± 1.620.24 ± 0.260.20 ± 0.160.61 ± 0.76
Stage II3.87% ± 1.54.55 ± 1.80.35 ± 0.390.22 ± 0.180.49 ± 0.35
Stage III6.15% ± 1.685.52 ± 2.060.35 ± 0.160.38 ± 0.190.67 ± 0.44
Stage IV14.06% ± 8.458.05 ± 1.761.00 ± 0.760.69 ± 0.341.24 ± 0.79

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CONCLUSION: Histomorphometric values of fibrotic tissue increase progressively in Ludwig’s stages of PBC, where non-invasive markers do not, and correlate positively with indirect serum markers of liver fibrosis.

Disclosure of Interest: None declared

P0012 THE NGF RECEPTOR P75NTR LEADS TO NEURAL HYPERTROPHY DURING THE DEVELOPMENT OF LIVER CIRRHOSIS AND MALIGNANT LIVER TUMORS

D. Hartmann1,*, S. Werscher1, R. Göß1, S. Teller1, M. Schlitter2, K. Becker2, H. Friess1, G.O. Ceyhan1

1Department of Surgery, 2Institute of Pathology, Technische Universität München, Munich, Germany

Contact E-mail Address:[email protected]

INTRODUCTION: The autonomic nervous system is the involuntary part of the peripheral nervous system and regulates the intestinal motor activity, smooth muscles and exocrine glands. Autonomic nerves that innervate the liver reach the organ via the hepatic hilum and run together with the portal vein, the hepatic artery and the bile duct. In the full clinical picture of liver cirrhosis, no parenchymal innervation can be detected. In addition, malignant liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC), are not innervated.

AIMS & METHODS: The aim of this work is the characterization of a possible hepatic neuroplasticity, including responsible neurotrophic factors. In the present work, a collective consisting of 103 patients (22 patients with normal liver tissue, 23 patients with liver cirrhosis, 45 patients with HCC and 13 patients with CCC) was examined for variations in nerve number and nerve size. In addition, growth factors, such as Growth-Associated Protein (GAP-43) and Nerve Growth Factor (NGF), as well as their receptors TrkA and p75NTR were investigated by immunohistochemistry and qRT-PCR in terms of their involvement in a possible hepatic neuroplasticity.

RESULTS: The multiple comparison of median nerve sizes of the examined entities showed a clearly significant difference. The largest nerves were discovered in HCC samples. However, no difference in neural density was detected. Furthermore, significant differences were observed for the high affinity NGF-receptor TrkA and the low affinity NGF-receptor p75NTR with regards to immunoreactivity and relative expression. The highest p75NTR expression was found in normal liver tissue and both, relative expression as well as immuno-reactivity, decrease with increasing nerve size.

CONCLUSION: The results of the present study suggest that the observed neural changes in the liver are related to active neural remodeling processes. The NGF receptor p75NTR seems to take on a key role in this context. Since p75NTR binds all neurotrophins with low affinity, further research is warranted concerning its involvement in the plasticity of hepatic nerves.

Disclosure of Interest: None declared

P0013 HIGH CONCENTRATION OF FIBROTIC AND INFLAMMATORY MARKERS AMONG PATIENTS WITH SCHISTOSOMAL LIVER DISEASES

E. Sinkala1,2, P. Kelly3,4, E. Sinkala1,2,*

1Internal Medicine, University of Zambia, 2Internal Medicine, TROPGAN, Lusaka, Zambia, 3Internal Medicine, Barts and London, Blizzard Institute, London, United Kingdom, 4Internal Medicine, University Teaching Hospital, Lusaka, Zambia, Lusaka, Zambia

Contact E-mail Address:[email protected]

INTRODUCTION: Worldwide the commonest cause of portal hypertension is cirrhosis, but in tropics it is schistosomiasis. Some parts of Zambia are hyper-endemic with prevalence of 77%. Hepatocellular function is preserved in hepatosplenic schistosomiasis hence prognosis is better than cirrhosis. Liver biopsy can confirm fibrosis but it is invasive.

AIMS & METHODS: This is an ongoing case control study involving 70 cases and 20 controls. All cases had varices and were negative for HIV, hepatitis B and C viruses. Hyaluran was used as a marker of liver fibrosis while TNF receptor 1, sCD14, IL1 beta, IL 6 and CRP were inflammatory markers.

We set out to investigate fibrotic and inflammatory makers in hepatosplenic schistosomiasis patients at the University Teaching Hospital, Lusaka, Zambia.

RESULTS: Eighty patients were evaluated and serology for schistosomiasis was positive in 74 (93%) and negative in 6 (7%). Hyaluran levels compared with controls were higher, p<0.001 (median 111.6ng/ml, IQR 39.1, 240.3). Inflammatory markers were elevated: TNF receptor 1 concentrations compared with controls were higher, p <0.001 (median 3150.1pg/ml (IQR 1703.2, 10460.0), sCD14 values were higher than in controls p<0.001, median 2365.0ng/ml (IQR1744.9, 3128.6). IL 1 beta values were higher than in controls p = 0.013, median 4.3pg/ml (IQR 0.8, 13.2) and so were IL 6 values p = 0.001 (median 15.26pg/ml, IQR 10.15, 38.13). Spearman’s rank correlation of hyaluran and TNF receptor 1 was positive (r = 0.44, p = 0.002) and so was hyaluran and IL6 (r = 0.251, p = 0.045).

CONCLUSION: Schistosomiasis is a leading cause of portal hypertension in Zambia and induces a liver fibrotic marker which could be used to assess disease severity. It seems hepatosplenic schistosomiasis also induces high levels of TNF receptor 1, sCD14, IL1 beta and IL6. These elevated markers could be due to bacterial translocation which needs to be confirmed by markers of bacterial translocation such as LPS.

Disclosure of Interest: None declared

P0014 LIVER FIBROSIS PREVENTION AFTER INTRAMUSCULAR ADMINISTRATION OF MATRIX METALLOPROTEINASE-8 ADENOVIRAL VECTOR IN A MODEL OF HEPATIC FIBROSIS

J. Garcia-Bañuelos1,*, E. Eden Oceguera-Contreras1, D. Gordillo-Bastidas1, A. Sandoval-Rodríguez1, B. Bastidas-Ramírez2, J. Gonzalez-Cuevas1, J. Macias-Barragan1, B. Belinda Gomez-Meda1, J. Armendáriz-Borunda1 on behalf of INNOVARE, Guadalajara, Jalisco, México

1Instituto de Biología Molecular y Terapia Génica, Centro Universitario de Ciencias de la Salud, 2Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico

INTRODUCTION: MMP-8 degrades preferentially collagen type I (collagen of higher proportion of hepatic fibrosis). We delivered MMP-8 gene in to the muscle, using an Adenovirus vector, protein is released systemically and is activated in the liver.

AIMS & METHODS: Our aim was to evaluate profibrogenic gene expression pattern and liver fibrosis prevention.

We used four groups of rats (n = 15): control; thioacetamide (TAA), induced-fibrosis; TAA+AdGFP; TAA+AdMMP8. At the beginning of the fifth week of TAA intoxication, administration of vectors in soleum muscle was accomplished. Sub-groups of rats (n = 5) at the end of first, second and third week after vector administration were sacrificed. Percentage of fibrosis, liver function, gene expression of MMP8, proinflammatory genes (IL1-beta, TNF-alpha), profibrogenic genes (collagen α1(I), CTGF and TGF-beta) and antifibrogenic genes (MMP1 and MMP9), were determined.

RESULTS: After 3 weeks of treatment: In the liver and serum, amount of MMP8 protein was sustained, fibrosis decreased up to 48%, proinflammatory genes expression was modified only at the end of the third week, profibrogenic gene expression decreased (Col α1(I) 4 times, TGF-beta 3 times and CTGF 2 times), antifibrogenic genes expression increased (MMP9 2.8 times and MMP1 10 times). According to Knodell score, a clearly diminution of inflammatory cells infiltration in comparison with counterpart animals treated with AdGFP, could be appreciated.

CONCLUSION: A single dose of AdMMP8 in muscle is enough in order to obtain a stable liver MMP8 protein expression and activity during 21 days. Degradation of collagen in the liver modifies pro and anti-fibrogenic gene expression allowing a restoration of hepatic architecture.

Disclosure of Interest: None declared

P0015 WHOLE-PROTEIN MASS SPECTROMETRY TO IDENTIFY CONGENITAL DISEASE OF GLYCOSYLATION IN END-STAGE LIVER DISEASE

J.C. Jansen1,*, M.van Scherpenzeel2, D.J. Lefeber2, J.P. Drenth1

1Gastroenterology and Hepatology, 2Laboratory of Genetic, Endocrine and Metabolic Disease, Radboud University Medical Center, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Congenital disorders of glycosylation (CDG) are a heterogeneous group of autosomal recessive metabolic diseases with a wide spectrum of clinical symptoms. Depending on localization of the defective protein, two types are distinguished (CDG-I; endoplasmatic reticulum and CDG-II; Golgi apparatus). Liver involvement is frequent in both groups and can even be predominant for some CDG-II variants. Abnormal glycosylation is seen in liver cirrhosis, probably resulting from affected liver synthesis. We hypothesized that mass spectrometry (MS) differentiates between secondary and bonafide genetic causes in end-stage liver disease.

AIMS & METHODS: To determine the effect of a diminished liver function on glycosylation we analyzed anonymous serum samples drawn from end-stage liver disease patients prior to their liver transplantation. As a first step we used transferrin isoelectric focusing (tIEF) to detect abnormal glycosylation. Selected samples were further analyzed with transferrin whole-protein MS to obtain a comprehensive readout of the glycosylation profile.

We also obtained serum from 100 patients with a presumed CDG. Patients with a predominant liver phenotype were selected for further analysis using exome sequencing for identification of the pathogenic mutation.

RESULTS: We collected 1065 serum samples and found an abnormal tIEF pattern in 30%. All abnormalities were mild and resembled a CDG-II pattern. MS of abnormal tIEF samples had increased fucosylation of transferrin and loss of one sialic acid.

We identified 18 patients with a phenotype resembling Wilson disease with liver fibrosis, elevated transaminases, low ceruloplasmin and liver copper accumulation. DNA is currently prioritized for exome sequencing. MS comparison of the Wilson disease-like patients and liver transplant patients showed that desialization is more abundant in Wilson disease-like patients and transferrin fucosylation is seen more often in liver transplant patients.

CONCLUSION: Whole protein MS enables differentiation between abnormal glycosylation secondary to liver failure and bonafide CDG. This can aid in the detection of CDG as a cause for liver pathology.

Disclosure of Interest: None declared

P0016 MICRORNA EXPRESSION PROFILE IN SIMPLE STEATOSIS AND NON-ALCOHOLIC STEATOHEPATITIS

K. Okamoto1,*, T. Okamoto1, T. Onoyama1, K. Miyoshi1, M. Kishina1, J. Kato1, S. Tokunaga1, T. Sugihara1, Y. Hara2, M. Koda1, K. Hino2, Y. Murawaki1

12nd. Dept. of Internal Medicine, Tottori Univ. School of Medicine, Yonago, 2Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are regarded as histological subtypes of non-alcoholic fatty liver disease (NAFLD). The distinctive pathological difference between SS and NASH is that NASH induces chronic liver inflammation and fibrogenesis, which can lead to liver cirrhosis. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression by repressing translation or degrading target mRNAs. Accumulating evidence indicates that miRNAs play important roles in various life functions including inflammation, metabolism, and fibrosis.

AIMS & METHODS: The purpose of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans. DD Shionogi (DS), Fatty Liver Shionogi (FLS), and FLS ob/ob mice were subjected as the normal control, SS model, and NASH model, respectively. Microarray analysis was used to assess 375 miRNA expression profiles in mouse liver tissue. Normalized miRNA expression ratios over ±2log2 between FLS and FLS ob/ob were identified as candidates. Real time PCR was used to check the reproducibility of the microarrays predicting miRNAs from 4 mice in each group. The putative miRNA target genes were predicted using the web-driven software DIANA microT-CDS. DAVID 6.7 was used to perform gene ontology annotation and KEGG pathway enrichment analysis. The putative miRNA expression profiles in human serum were also examined in every 10 patients with asymptomatic gallbladder stones, SS, and NASH.

RESULTS: In microarray analysis, 18 miRNAs were identified as candidates. Among the 18 miRNAs, 6 showed good expression ratio reproducibility in real time PCR and were confirmed to express commonly between mice and humans. The expression levels of miR-200a and miR-200b increased in the order of normal control, SS, and NASH. miR-1 was downregulated in NASH. miR-376c, miR-409, and miR-411 showed potent high expression in SS, over 30-fold of DS. KEGG pathway analysis indicated that the strongly expressed miRNAs in SS (miR-376c, miR-409, and miR-411) had multiple targets in the TGF-β signaling pathway including TGFR, smad 2, 3, and 4. The analysis suggests that miR-376c, miR-409, and miR-411 may protect liver fibrosis through silencing the TGF-β signaling pathway. In human serum, hierarchical clustering analysis of the putative miRNA expression also showed clearly different expression profiles between SS and NASH.

CONCLUSION: The expression profiles of 6 miRNAs were different between SS and NASH models. Some potential target genes of the putative miRNAs were found to be involved in the TGF-β signaling pathway. Furthermore, the putative miRNA expression profiles in human serum were also clearly different between SS and NASH patients. These miRNAs have high potential as biomarkers to distinguish the fate of NAFLD patients and contribute to further research in the pathogenesis and treatment of NASH.

Disclosure of Interest: None declared

P0017 PROTECTIVE EFFECTS OF MELATONIN ON THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS

K. Celinski1,*, G. Czechowska 1, A. Korolczuk2, G. Wójcicka3, J. Dudka4, A. Bojarska-Junak5, A. Mądro1, H. Cichoż-Lach1

1Gastroenterology, 2Department of Clinical Pathomorphology, 3Department of Clinical Pathophysiology, 4Medical Biology, 5Clinical Immunology, MEDICAL UNIVERSITY OF LUBLIN, Lublin, Poland

Contact E-mail Address:[email protected]

INTRODUCTION: The aim of the present study was to determine the effect of melatonin on liver fibrosis induced with long-term administration of thioacetamide (TAA) in an animal model. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis, i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and direct markers represented by proinflammatory cytokines such as interleukin 6 (IL-6), interleukin beta 1 (IL-beta1), tumour necrosis factor alpha (TNF-alpha, transforming growth factor beta 1 (TGF-beta1) and platelet-derived growth factor (PDGF- AB). Moreover, parameters of oxidative stress were determined, i.e. concentrations of oxidised glutathione (GSSG) and reduced glutathione (GSH), activity of paraoxonase 1 (PON-1), an enzyme of antioxidative properties. Inflammatory changes and extent of fibrosis were evaluated histologically.

AIMS & METHODS: Experiments were carried out in Wistar rats. Animals were divided into 4 groups, 8 individuals each: group I- controls receiving drinking water ad libitum for 12 weeks, group II – TAA, 300 mg/L ad libitum for 12 weeks, group III- melatonin, 10 mg/kg b.w. administered intraperitoneally (IP) daily for 4 weeks, group IV – TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. administered IP daily for 4 weeks.

RESULTS: Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin (IV) compared to the group receiving only TAA (II). Immunoenzymatic findings regarding the effect of melatonin on concentration of proinflammatory cytokines (Il-6, Il-beta1, TNF-alpha, TGF-beta 1, PDGF-AB) confirmed these data.

CONCLUSION: Biochemical examinations in liver homogenates revealed statistically significant improvement of oxidative stress parameters (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin (IV). Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was found to be increased in liver homogenates and serum in the group receiving TAA followed by melatonin (IV) compared to the TAA group (II). Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

Disclosure of Interest: None declared

P0018 ROLE OF GAMMA-KETOALDEHYDES AS NOVEL MEDIATORS OF EXPERIMENTAL FIBROGENESIS AND STELLATE CELLS ACTIVATION

L. Longato1,*, K. Rombouts1, D. Dhar1, S. Davies2, J. Roberts2, T. V. Luong1, M. Pinzani1, K. Moore1

1UCL Institute for Liver & Digestive Health, University College London, London, United Kingdom, 2Pharmacology, Vanderbilt University, Nashville, United States

Contact E-mail Address:[email protected]

INTRODUCTION: Reactive lipid aldehydes formed during lipid oxidation such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSCs) to a pro-fibrogenic phenotype. γ-Ketoaldehydes (γ-KAs) are highly reactive lipid aldehydes formed during oxidation of arachidonic acid or as a by-product of the cyclo-oxygenase pathway. γ-Ketoaldehydes are ∼100x more reactive than HNE, and form protein adducts and cross-links. Increased circulating concentrations of proteins cross-linked to γ-ketoaldehydes are present in patients with alcoholic liver disease.

AIMS & METHODS: The aim of this study was to investigate whether one specific γ-ketoaldehyde, namely levuglandin E2 (LGE2), can induce activation of HSCs. Cultured activated, serum-starved primary mouse and human HSCs were exposed to various concentrations (0.5 pM-5 µM) of levuglandin E2 (LGE2) for up to 48 hours. Endpoints measured included proliferation (BrdU incorporation), cytotoxicity (lactate dehydrogenase (LDH) release and tetrazolium (MTS) reduction), RNA expression (qRT-PCR), protein expression (Western Blot), and collagen secretion in conditioned medium (SirCol assay).

RESULTS: HSCs exposed to LGE2 exhibited profound cytotoxicity at 5 μM concentration, as indicated by LDH leakage and reduced MTS. This was mediated by an induction of apoptosis, indicated by an increase in PARP cleavage, occurring as early as 8 hours after LGE2 exposure. However, at lower, non-cytotoxic doses (ranging from 50 pM-500 nM, with a maximum effect observed at 0.5 nM), LGE2 promoted HSC activation as indicated by increased expression of α-smooth muscle actin and vimentin, as well as increased proliferation and collagen secretion. In addition, LGE2 exposure promoted sustained activation of signalling pathways, as indicated by the increased phosphorylation of the kinases ERK1/2 and JNK, as well as an increase in mRNA levels of chemokines such as IL-8 and MCP-1. We are currently investigating the potential protective action of administration of a γ-ketoaldehyde scavenger in an animal model of hepatic fibrosis.

CONCLUSION: γ-Ketoaldehydes represent a newly identified class of activators of HSCs in vitro, which are biologically active at concentrations as low as 50 pM.

Disclosure of Interest: None declared

P0019 NONINVASIVE SERUM FIBROSIS MARKERS IN COMPARISON WITH GRADING AND STAGING IN CHRONIC HEPATITIS

M. Abdollahi1,*, A. Pouri2, M. Somi2

1Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, 2Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Islamic Republic Of

Contact E-mail Address:[email protected]rD

INTRODUCTION: Chronic hepatitis is defined as a necroinflammatory disease of the liver continuing for at least six months. The aim of this study was to evaluate the role of noninvasive fibrosis markers by assessing the association among grading and staging and these diagnostic parameters in patients with chronic hepatitis.

AIMS & METHODS: We retrospectively studied 221 patients with chronic hepatitis between 2011 and 2013. Routine biochemical indices and serum fibrosis indexes such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were determined, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Receiver operating characteristic curve (ROC) analysis was conducted to compare diagnostic accuracies of these markers for prediction of significant fibrosis.

RESULTS: We identified 221 liver biopsies from chronic hepatitis patients with contemporaneous laboratory values for imputing AAR, APRI and FIB-4. From all, 135 males (61.1%) and 86 females (38.9%), with the mean age of 39.6±14.4 were studied. FIB-4, APRI and AAR were correlated significantly with the stage of fibrosis, with a higher correlation coefficient than other markers in the patients with Hepatitis B (r =  0.46), C (r =  0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) was superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy.

CONCLUSION: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Disclosure of Interest: None declared

P0020 REVEALING THE MOLECULAR MECHANISM OF RAT LIVER RESPONSE TO LONG-TERM OMEPRAZOLE TREATMENT WITH BIOINFORMATICS APPROACH

S. Vakal1, E.A. Virag2, K. Dvorshchenko1, L. Ostapchenko1,*

1ESC "Institute of Biology", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, 2University of Pecs, Pecs, Hungary

Contact E-mail Address:[email protected]

INTRODUCTION: Omeprazole is a widely prescribed acid-suppressing drug available for clinical use for 25 years. Despite well-studied adverse effects of short-term omeprazole treatment, underlying mechanisms of some hepatotoxic effects of long-term injection of high omeprazole doses (e.g. development of oxidative stress and histopathologic changes [1]) are not understood. Transcriptome analysis is a powerful tool for elucidation of possible mechanisms of cellular response to different conditions on molecular level. Bioinformatics approach is suitable for processing of large datasets, prediction of possible regulatory circuits and generation of hypotheses on involved molecular mechanisms [2].

AIMS & METHODS: The purpose of the research was to find out possible molecular mechanisms of rat liver cells response to long-term injection of omeprazole.

GSE8858 dataset and GPL2454 platform description were downloaded from NCBI Genome Expression Omnibus database. Gene expression data from livers of rats treated with 30 mg/kg and 415 mg/kg for 1 and 25 days were compared in order to reveal differentially expressed genes (DEGs). DEGs were determined with GEO2R tool on the basis of t-criterion and adjusted p value. Gene ontology (GO), pathway enrichment analyses and building of protein-protein interactions (PPI) network were performed with STRING 9.1. Prediction of miRNAs and cis-elements for DEGs was carried out with WebGestalt toolkit. Clusters were identified by K-means analysis in ClusterONE. All networks were visualized using Cytoscape.

RESULTS: In total 79 DEGs (21 up- and 58 down-regulated) and 87 DEGs (41 up- and 46 down-regulated) were identified in samples of rat livers treated with 30 and 415 mg/kg during 25 days, respectively. At the same time 22 genes with similar pattern of expression (9 up- and 13 down-regulated) were found for both types of dosage. Among them are Arntl, Cdk1a, Chka, Gpam, Litaf, Slc2a5, Usp2 etc. Enrichment in such GO terms was revealed: cell cycle, mitosis, nuclear division, lipid metabolism. Only genes involved in lipid metabolism were up-regulated, while others were suppressed. Genes involved in PPAR signalling pathway were found to be differentially regulated upon 25-day treatment with omeprazole. Most of DEGs (51 genes) were of cytoplasmic proteins (housekeeping genes). PPI networks were constructed for 98 proteins and 102 interactions revealed. The optimal amount of clusters was equal to 3. MiRNA-9, 17-5p, 20A, 20B, 106A, 106B, 200B, 200C, 429, 506 and 519D were found to be involved in regulation of revealed DEGs. 24 probable cis-elements were predicted for promotors of identified DEGs.

CONCLUSION: Thus, long-term treatment of rats with omeprazole is associated with changes in expression of housekeeping genes: down-regulation of genes involved in cell-cycle process and cellular division, up-regulation of genes involved in lipid metabolism, and changes in expression of PPAR signalling pathway genes.

REFERENCES

1. Dvorshchenko KO, Bernyk OO, Dranytsyna AS, et al. Influence of oxidative stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term gastric hypochlorhydria and administration of multiprobiotic Symbiter. Ukr Biokhim Zh 2014; 85: 114-123.

2. Shen B, Zhou S, He Y, et al. Revealing the underlying mechanism of ischemia reperfusion injury using bioinformatics approach. Kidney Blood Press Res 2013; 38: 99-108.

Disclosure of Interest: None declared

P0021 MORPHOLOGICAL AND FUNCTIONAL CHANGES OF LIVER MACROPHAGES DURING THE PROGRESSION OF NONALCOHOLIC STEATOHEPATITIS (NASH)

S. Bruzzi'1,*, S. Sutti1, A. Jindal1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1

1Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Recent reports indicate that both human and experimental NASH is characterized by an increase in hepatic monocyte infiltration and that macrophages have an important role in regulating the disease evolution. However, little is known about the functional changes occurring in liver macrophages during the progression of NASH.

AIMS & METHODS: NASH was induced in C57BL/6 mice by feeding a methionine-choline deficient (MCD) diet up to 8 weeks.

RESULTS: Mice receiving the MCD diet showed a progressive worsening of parenchymal damage and lobular inflammation, while liver fibrosis was evident only after 8 weeks of treatment. Hepatic F4/80-positive macrophages increased in parallel with the disease progression. In the early phases of NASH after 4 weeks on the MCD diet these cells prevalently expressed markers of inflammatory monocytes such as Ly6C and CD11b, but the prevalence of Ly6C+/CD11b+ cells decreased by extending the treatment up to 8 weeks. This paralleled with a lowering in the monocyte chemokines CCL1/CCL2 and their receptors CCR8/CCR2. We observed that the expression of the macrophage M1 activation markers iNOS and IL-12 also peaked at 4 weeks and declined thereafter. No appreciable changes were instead observed in the levels of M2 polarization markers arginase-1 and MGL-1. Histology revealed that the macrophages accumulating in advanced NASH (8 weeks MCD) were enlarged, vacuolized and formed small aggregates. Immunofluorencesce showed that these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting that they have phagocytosed apoptotic bodies derived from dying fat-laden hepatocytes. At flow cytometry, enlarged macrophages were characterized by a weak Ly6C/CD11b expression and by a low IL-12 production. On the other hand, these cells showed an enhanced expression of the anti-inflammatory mediators IL-10 and annexin A1. The production of the pro-fibrogenic cytokine TGF-β was increased in the macrophages obtained from NASH livers, irrespective of the cell phenotype.

CONCLUSION: Altogether, these data indicate that during the progression of NASH liver macrophages down-modulate their pro-inflammatory phenotype in parallel with the phagocytosis of apoptotic hepatocytes and acquired anti-inflammatory properties.

This work has been supported by a grant from the Fondazione Cariplo (Milan).

Disclosure of Interest: None declared

P0022 MICRORNA-27B DEVELOP THE FATTY LIVER FORMATION AND INSULIN RESISTANCE AT THE SAME ONSET

T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, Y. Eguchi2, K. Wada3, A. Nakajima1

1gastroenterology and hepatology, Yokohama city university, yokohama, 2internal medicine, saga university, saga, 3 Pharmacology, Osaka University Graduate School of Dentistry, Oosaka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in Asia Pacific region is close to 12–24%, while in Western countries is about 20–30%1). And nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. In spite of its high prevalence, up till now there is no proven effective treatment for NAFLD3). Along with the “obesity epidemic,” the worldwide prevalence of NAFLD is increasing rapidly and is generally assumed to be a consequence of obesity-induced insulin resistance 2). On the other hand, not all obese individuals are insulin resistant, nor are all insulin-resistant individuals obese 4). MicroRNAs (miRs) are a class of small non-coding RNAs that function to control gene expression by inducing the degradation or inhibiting the translation of mRNA through an association with its 3’-untranslated region (3’UTR). Although miRs play a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM), detailed mechanisms of this pathogenesis remain unclear.

AIMS & METHODS: We found that miR-27b increased in liver biopsy specimens of NAFLD patients with DM using microarray analysis, as compared with controls. The aim of this study was to investigate whether overexpression of miR-27b in liver could cause fatty liver formation and insulin resistance, and to examine the mechanism of NAFLD and DM onset in a murine model.

Five-week-old male C57BL/6J mice were randomized into 2 groups (n = 16 mice): basal diet (BD)-fed control mimic (BD-Con, n = 4), BD-fed miR-27b-mimic (BD-miR-27b, n = 4). In this study, miR-27b mimic is injected intravenously at 7mg/kg. We comfirmed the target genes of miR-27b using quantitative RT-PCR analysis. Insulin serum concentrations were measured by a local laboratory for clinical examinations. As an alternative method for assessing insulin resistance (IR), the homeostasis model assessment of IR (HOMA-IR) was calculated using the following formula: fasting insulin (mU/mL) plasma glucose (mg/dL) / 405.

RESULTS: BD-miR-27b significantly showed steatosis using oil red o staining and increased hepatic tryglyceride content, as compared with BD-Con. In the analysis of fat accumulation-related gene expression, hepatic Peroxisome proliferator-activated receptor α (PPARα) and Microsomal triglyceride transfer protein (MTTP) are significantly decreased. At the same time, BD-miR-27b showed hyperinsulinemia and insulin resistance. In the analysis of insulin resistance-related gene expression, hepatic Insulin receptor substrate 1 (IRS-1) is significantly decreased.

CONCLUSION: miR-27b controls multiple gene levels that are involved in fat accumulation and insulin resistance, resulting in the NAFL and DM pathology. These results propose a therapeutic approach for NAFL and DM by targeting miR-27b.

REFERENCES

1) Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia–Pacific region: executive summary. J Gastroenterol Hepatol 2007; 22: 775–777.

2) Clark JM, Brancati FL and Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649–1657.

4) Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity: European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166–1173.

Disclosure of Interest: None declared

P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER REGENERATION IN A RABBIT MODEL

F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van Gulik1

1Surgery, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase future remnant liver volume in patients requiring extended resections. Reversible PVE is of interest when generating sufficient hypertrophy while preserving the embolized liver lobe. The concept of reversible PVE requires an absorbable embolization material.

AIMS & METHODS: The aim of this study is to modulate lysis time of a fibrin-glue based embolization material while using different concentrations of Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG.

PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5 groups:

• Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), n = 4)

• Fibrin glue with Aprotinin (FG700KIU, n = 5)

• Fibrin glue with Aprotinin (FG500KIU, n = 5)

• Fibrin glue with Aprotinin (FG300KIU, n = 5)

• Fibrin glue without Aprotinin (FG-Aprot, n = 5)

The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight ratio of NEL were evaluated.

RESULTS: Data were compared with a previous series using a permanent embolization material, i.e. polyvinyl alcohol + coils (PVAc), showing complete and permanent occlusion of the embolized portal vein branch in all rabbits after 7 days.

FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of the FG+1000KIU Aprotinin group was still occluded and showed a hypertrophy response comparable to the PVAc group. The group of FG 700KIU Aprotinin survived 14 days and in two of the five rabbits, the embolized portal vein was recanalized at sacrifice. The hypertrophy response in these rabbits was not different from the PVAc group. The rabbits with FG 500KIU and 300KIU Aprotinin were sacrificed at day 49. In the group with FG 500KIU Aprotinin, 4 out of 5 showed recanalization of the cranial portal branches. In the group with FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups showed hypertrophy response rates not different compared to the PVAc group.

CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU Aprotinin resulted in 70% reversible embolization with a hypertrophy response comparable to the PVAc group.

Disclosure of Interest: None declared

P0024 TRANSPLANTATION OF HUMAN AMNION-DERIVED MESENCHYMAL STEM CELLS AMELIORATES CARBON TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS

K. Kubo1,*, S. Ohnishi1, N. Sakamoto1

1Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease caused by a variety of factors, such as viral infections, alcohol, drugs and chemical toxicity. The only effective available treatment for end stage liver fibrosis is transplantation; however, due to the lack of donors, complications and transplant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs) have been reported to be a valuable cell source in cell therapy. Recently, bone marrow- or adipose tissue-derived MSCs have been reported to be effective in the treatment of liver fibrosis. In addition, several studies have shown that MSCs can be easily isolated from human amnion, and a large amount of cells can be obtained. Therefore, we examined the effects of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.

AIMS & METHODS: All pregnant women gave written informed consent, and amnion was obtained at Cesarean delivery. hAMSCs were isolated by collagenase treatment, and expanded with culture medium containing fetal bovine serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a week for 7 weeks. At 3 weeks, hAMSCs (1×106 cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative RT-PCR were performed.

RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area and deposition of type I collagen. In addition, hAMSC transplantation significantly decreased the number of α-SMA-positive hepatic stellite cells and and CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expression of α-SMA was significantly decreased in the liver of hAMSC-treated rats, and mRNA expression of type I collagen, TGF-β and IL-1β tended to be decreased by hAMSC transplantation.

CONCLUSION: Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through inhibition of inflammatory reaction. hAMSC would be considered as a new cell source for the treatment of liver fibrosis.

Disclosure of Interest: None declared

P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER CELLS IN AN ANIMAL MODEL OF NAFLD

V. Lembo1,*, G. Mazzone1, G. D'Argenio1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine and Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most common liver disease in Western countries, is pathogenetically related to a sedentary lifestyle as well as to poor quality diet characterized by an excessive energy intake including high fatty foods and high amounts of fructose, the so-called Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of triglycerides. Vitamin D in addition to the effects on lipid metabolism, plays other biological functions, among which a trophic effect on human cultured cells.

AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by Western Diet, the relationship between body weight, liver weight and grade of steatosis; and if these parameters are modified by vitamin D supplementation. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD); WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment was conducted for 6 months. Weekly, the rats, body weight was recorded. At sacrifice, livers were excised and weighed and samples were stored at -80°C. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis was numerically scored following semi-quantitative pathological standard.

RESULTS: During the experiment the increase of body weight was similar in the three groups. In the two groups fed with WD liver weight was significantly higher than SD group (p<0.01). A positive correlation between body weight and liver weight was observed in WD groups (p<0.0001). The liver/body weight ratio was significantly higher in WD and WDVitD groups than SD: 2.9±0.05, 2.8±0.07 and 2.0±0.04, respectively; p<0.001). Steatosis was present in 61% and 21% of hepatocytes in WD group and WDVitD group, respectively, and absent in SD group. No correlation was found between the grade of steatosis and liver or body weight nor between the grade of steatosis and liver/body weight ratio. Although vitamin D supplementation reduced the degree of steatosis, liver/body weight ratio in WDVitD group was similar to WD group.

CONCLUSION: In a rat model of NAFLD induced by WD the presence and extent of steatosis are independent from body weight. Interestingly and unexpectedly, in WD groups the supplementation with vitamin D reduces liver steatosis but not liver weight: this sustains the hypothesis of a trophic effect of vitamin D on liver cells.

Disclosure of Interest: None declared

P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT MODEL OF NAFL

G. Mazzone1,*, V. Lembo1, G. D'Argenio1, M. Guarino1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine and Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease (NAFLD) rise to become the most common cause of chronic liver disease in Western countries. It is known that insulin resistance and type 2 diabetes mellitus (T2DM) have an important role in the pathogenesis of obesity and NAFLD. A growing body of evidence points to a linked and potentially causative relationship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.

AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin D3 supplementation is able to modulate the liver effects and glucose homeostasis of a westernized diet, high in fat and fructose, in an animal model of NAFL without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23 IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6 months. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Insulin resistance was determined according to the Homeostasis Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evaluated according to Brunt EM et al.

RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while in WDVitD group only 27% of hepatocytes contained fat. In WD group HOMA-IR was significantly higher than in SD (41.9±8.9 vs 6.17±1.3, p<0.01) and it was reduced by vitamin D supplementation in WDVitD group (41.9±8.9 vs 19.4±5.2, p<0.05). Interestingly SD and WDVitD rats were not diabetic (98.7±8.0 and 103.2±6.1, respectively) while all rats in WD group were diabetic (139±9.6) with glycemic values significantly higher than SD (p<0.01) and WDVitD (p<0.05).

CONCLUSION: These results suggest that a daily supplementation of vitamin D3 is able to improve insulin sensitivity and to prevent the development of diabetes and hepatic steatosis in WD rats.

Disclosure of Interest: None declared

P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE

S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3, H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1

1Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research Center for Post-genome Science and Technology, 4Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Sphingomyelin (SM) is a major component in lipid microdomains, and SM is synthesized from ceramide by the action of SM synthase (SMS). We have recently reported that mice deficient for SMS2 are resistant to high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem 2011:286;28544). In this study, we examined the relationship between SM and ceramide molecular species and the development of NAFLD and insulin resistance in human.

AIMS & METHODS: Non-alcoholic students of our university with body mass index (BMI) ≥ 35 kg/m2 at the regular physical checkup in 2013 were enrolled, and volunteer students with BMI of 20-22 kg/m2 were set as a control group. Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0, C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver enzymes, lipids and insulin resistance were measured by blood examination. Abdominal ultrasound was performed to confirm the existence of fatty liver, and body composition including percent body fat (PBF) was measured by bioimpedance analysis.

RESULTS: The levels of total SM and ceramide were not altered in obese group (19-28 y.o., n = 12), compared with control group (18-27 y.o., n = 11). The concentrations of SM C18:0 and C24:0 in the obesity group were significantly higher than in the control group. Moreover, in the obese group, SM C20:0 and C22:0 tended to be higher than in the control group. In the analysis of total 23 cases, the serum levels of SM containing saturated fatty acids positively correlated with PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing unsaturated acyl chain and almost all ceramide species did not correlate with those items.

CONCLUSION: The present study demonstrated that the serum levels of SM species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are correlated with liver function and insulin resistance, suggesting that distinct SM species are involved in the development of NAFLD and insulin resistance.

Disclosure of Interest: None declared

P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18 AND CONTROLLED ATTENUATION PARAMETER (CAP) IN HEALTHY POPULATION

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutrição e metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative for the diagnosis of NAFLD, especially NASH.

AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy individuals with and without steatosis. Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis compared with US and CAP was assessed using AUROC.

RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass index) were 52.6±17.1 years and 28.2±4.9 kg/m2, respectively; 25% had a normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis on ultrasound was 52.1%.

The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respectively. Median CK-18 were elevated in patients with vs. without hepatic steatosis by ultrasound: 33.4 [IQR: 25–151] vs. 73.7 [IQR: 25–508] U/L, p <0.0001.

CK-18 significantly correlated with steatosis (ρ = 0.40), ALT (ρ = 0.40), CAP (ρ = 0.38), triglyceride (ρ = 0.32), waist circumference (ρ = 0.30), HDL (ρ = -0.28), AST (ρ = 0.27), LDL (ρ = 0.26), total cholesterol (ρ = 0.21) and the number of metabolic syndrome criteria (ρ = 0.29), but not with LSM or BMI.

The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of 243 dB/m) were 0.78 (95% CI = 0.71–0.86) and 0.74 (95% CI = 0.65–0.82), respectively.

CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151, with a very large range. It showed a good discriminating capacity for diagnosing steatosis.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI) AND ULTRASOUND

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, A. Carvalho3, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

INTRODUCTION: The fatty liver index (FLI) derived from an Italian population includes serum triglycerides, serum gamma-glutamyltransferase, body mass index (BMI) and waist circumference. It has been used as a noninvasive measure of hepatic steatosis (HS), but has not been widely validated and not examined in the Portuguese population.

AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult population by fatty liver index (FLI) and correlate with the ultrasound findings; validate FLI for prediction of fatty liver in the Portuguese population.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI. Performance of FLI for diagnosing steatosis compared with US was assessed using AUROC.

RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circumference and BMIs were 50.5±18.4 years, 94.4±12.7 cm and 26.9±4.7 kg/m2, respectively; 43% were overweight and 22% were obese. The median of FLI was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.

Using the FLI, 27.6% of subjects had HS (FLI > 60), 41.8% had no HS (FLI < 30) and 30.6% were not classifiable (FLI 30-60). However, these cut-offs proposed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI <30 exhibited HS on ultrasound and 13.4% of subjects with FLI > 60 showed no steatosis. For the FLI, the area under the ROC curve was 0.88 for the diagnosis of HS.

There was a significant correlation (p < 0.01) between the FLI and the following variables: weight (ρ = 0.80), waist circumference (ρ = 0.74), presence of steatosis (ρ = 0.65), triglycerides (ρ = 0.58), BMI (ρ = 0.51), ALT (ρ = 0.43), GGT (ρ = 0.39), HDL (ρ = -0.36), age (ρ = 0.33), female sex (ρ = -0.33), insulin (ρ = 0.29), AST (ρ = 0.28), LDL (ρ = 0.24) and total cholesterol (ρ = 0.22). No correlation was found with physical activity.

CONCLUSION: FLI could accurately identify hepatic steatosis in the general Portuguese population. The calculation of FLI may be useful to suggest the possibility of the presence of steatosis and indicate the need for an abdominal ultrasound.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0030 “NORMAL” CONTROLLED ATTENUATION PARAMETER (CAP) VALUES: A POPULATION-BASED STUDY OF HEALTHY SUBJECTS

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. The normal range of controlled CAP values needs to be explored in clinical and anthropometrically diverse healthy subjects. A recent study has shown an association of CAP with BMI and the number of metabolic syndrome criteria.

AIMS & METHODS: Aim: define the normal range of CAP values in healthy subjects and evaluate the associated factors.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. CAP was performed using Fibroscan in 134 healthy subjects, without fatty liver on ultrasonography or positivity serology for HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.

RESULTS: From 134 consecutive individuals studied (66 males), 4 were excluded due to failure/unreliable liver stiffness measurements (LSM). The mean age and BMIs (body mass index) were 46.9±18.0 years and 24.9±3.5 kg/m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were obese. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3 dB/m, respectively. Men had a higher mean CAP value than women (mean±SD: 213.1±47.1 dB/m versus 191.8±47.8 dB/m, respectively; p = 0.012).

CAP significantly correlated with gender (ρ = 0.22), age (ρ = 0.22), waist circumference (ρ = 0.33), BMI (ρ = 0.22), alcohol consumption (ρ = 0.25), systolic blood pressure (ρ = 0.27), ALT (ρ = 0.27), fasting glucose (ρ = 0.24) and the number of metabolic syndrome criteria.

After allowance for potential confounders, CAP was not independently associated with BMI or other risk factors for nonalcoholic fatty liver disease.

CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy subjects and is not associated with BMI or the number of metabolic syndrome criteria.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL

T.J. G. Gevers1,*, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4, J.P. Drenth1

1Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology, 4Nephrology, RadboudUMC, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Several trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and possibly enhances risk for adverse events.

AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial) was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We excluded patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2. Primary outcome was change in liver volume, secondary outcomes were changes in kidney volume, eGFR, symptom relief and health-related quality of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within-group differences.

RESULTS: We included 43 ADPKD patients with polycystic liver disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver volume decreased from 4,859 ml to 4.595 ml (-3.1%;p<0.001), and median kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p = 0.006). eGFR declined 3.5% after the first injection and remained stable up to study end. Lanreotide significantly relieved postprandial fullness, shortness of breath and abdominal distension, but had no effect on any of the EuroQol-5D dimensions. Three participants had a suspected episode of hepatic or renal cyst infection during the study.

CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting lanreotide, but stabilized thereafter.

Disclosure of Interest: None declared

P0032 THE EFFECTS OF POLY-UNSATURATED FATTY ACIDS (PUFAS) IN A RODENT NUTRITIONAL MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)

V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1

14th Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

INTRODUCTION: NAFLD and subsequent NASH are probably the most common chronic liver diseases in western countries and have a high risk of development of liver cirrhosis associated with high morbidity and mortality.

AIMS & METHODS: The aim of the study was to determine effects of administration of PUFAs in the MCD dietary model of NASH and to assess the potential anti-inflammatory role of PUFAs in the pathogenesis of NASH.

For 6 weeks were male mice fed either with MCD or with chow. There were 4 groups of animals. Both experimental and control groups received from the beginning either PUFAs or saline. Detailed liver histology, serum biochemistry, total lipid and fatty acids compound, adiponectin and leptin levels were determined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were measured.

RESULTS: Feeding with MCD resulted in histopathological changes of NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP). Administration of PUFAs led to significant decreases of total animal and liver weight in MP. PUFAs also decreased cholesterol levels (P<0.001), ALT (P<0.01) and AST levels (P<0.01). MP developed significantly less pro-inflammatory cytokine profile, had lower leptin (P<0.01) and higher adiponectin levels (P<0.01) than controls. Administration of PUFA led also to lower serum concentrations of saturated and monounsaturated FA and to higher serum concentrations of polyunsaturated FA in MP. Total lipid content of liver was significantly lower in MP.

CONCLUSION: We conclude that PUFAs may play a causal role in the pathophysiology of NASH. In summary, PUFAs have favorable effects on histopathological changes, serum markers of liver damage, fatty acid compound and show anti-inflammatory properties. We expect that PUFAs may represent a promising way in prevention and treatment of this increasingly common disorder.

Disclosure of Interest: None declared

P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

W. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1, Y. Liu1,*

1Department of Gastroenterology, 2Institute of Clinical Molecular Biology & Central Laboratory, Peking University People's Hospital, Beijing, China

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by a broad spectrum of hepatic pathology that is closely linked to obesity and ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and even cirrhosis. NAFLD is recently believed to be under the influence of the gut microbiota, which may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein.

AIMS & METHODS: We explored the composition of gut bacterial communities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina next-generation sequencing.

RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that most of the microbiota samples were clustered by disease status. Differences were abundant at phylum, family, and genus levels between NAFLD and healthy subjects. Lentisphaerae at phylum level was significant higher in NAFLD microbiota. Among those taxa with greater than 0.1% average representation in all samples, five genera including Alistipes and Prevotella were the genus types exhibiting significant higher level in healthy microbiota, while genera Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in NAFLD microbiota. In addition, lymphocyte profiles (CD4+T cell and CD8+T cell) and proinflammatory cytokines (TNF-α, IL-6 and IFN-γ) in gut biopsies of patients and healthy controls was analyzed to monitor the inflammation caused by dysbiosis microbiota. The levels of CD4+ T cells and CD8+ T cells were lower in NAFLD patients compared with healthy subjects, and the proinflammation cytokine TNF-α, IL-6 and IFN-γ showed high level in NAFLD patients. What was more, irregular arrangements of microvilli and widening of the tight junction were observed in gut mucosa of the NAFLD patients by transmission electron microscope.

CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD microbiota, decreased numbers of CD4+T cells and CD8+T cells, and increased levels of TNF-α, IL-6 and IFN-γ in gut mucosa of NAFLD patients suggest a role for gut microbiota in the gut inflammation and the dysregulated gut immunity, which promote pathogenesis of NAFLD. We postulate that the distinct composition of the gut microbiome among NAFLD and healthy controls could offer a target for intervention or a marker for disease.

REFERENCES

1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab 2013; 24: 537-545.

2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-127.

Disclosure of Interest: None declared

P0034 ASCITIC FLUID LACTOFERRIN FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS

A.A. Ghweil1,*

1TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY OF MEDICINE EGYPT, Qena, Egypt

Contact E-mail Address:[email protected]

INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This procedure is operator-dependent and lysis of PMNs during transport to the laboratory may lead to false-negative results. Furthermore, ascitic fluid culture is insensitive and leads to delays in diagnosis. The aim of this study was to assess the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to identify a cut-off level that can be used for future development of a rapid bedside test.

AIMS & METHODS: Sixty ascites samples from cirrhotic patients were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC concentrations were determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or greater with or without a positive culture was used for diagnosis of SBP.

RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/mL; compared with non-SBP samples (median, 39 ng/mL P < .001). The sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%, respectively. The area under the receiver operating characteristic curve was 0.98. Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis

CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis.

Disclosure of Interest: None declared

P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS

C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D. I. Gheonea1, I. Rogoveanu1

1Gastroenterology, UMF CRAIOVA, Craiova, Romania

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex treatable malignancies as its management is dependent on the stage of the underlying condition – liver cirrhosis. An early diagnosis assures best curative chances, as liver resection or transplantation have good survival rates in the general population. Computer aided diagnostic and prognosis (CADP) models are currently being developed for a number of malignancies to help clinicians manage cases based on individual needs of the patients rather than general statistics.

AIMS & METHODS: Our aim was to develop a CADP based on our previous work involving artificial neural networks (ANN) [1] for successfully diagnosing early HCC cases and better prognosticate their evolution, based on a set of criteria in accordance with current guidelines.

Ethical clearance was obtained from the local board and 107 consecutive patients with previously diagnosed liver cirrhosis signed informed consents for entering the study, between January 2009 and February 2010. Clinical and demographic parameters (age, sex, body mass index, waist circumference, type of viral infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein thrombosis, size and number of possible tumors), elastography data (strain ratio, complexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular second moment, correlation) and stiffness value (FibroScan) were collected and imputed in the CADP. For patients with clear liver tumors contrast-enhanced ultrasound was performed and time-intensity curve parameters were calculated and fed to the ANN system: peak enhancement, time to peak, rise time, fall time, mean transit time, area under the curve. We have followed the 4-year incidence of HCC patients in tumor-free cases and assessed the evolution when any formation, either regeneration nodule or early HCC was found.

RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules [median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm (min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per patient: 1 (min: 1, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration nodules based on clinical, laboratory and imaging data. A total of 28 patients also developed HCC in the four-year follow-up period; the system correctly predicted high possibility for HCC occurrence in 26 of these patients (92.85%), while giving high estimates for HCC in another 16 patients that remained cancer-free until now.

CONCLUSION: We could successfully predict the rate of malignancy in cirrhotic patients by using a novel CADP system. We believe that such tools may become worthy aids to clinical management of patients with various types of digestive pathologies.

REFERENCES

1. Streba CT, et al. Using contrast-enhanced ultrasonography time-intensity curves as classifiers in neural network diagnosis of focal liver lesions. World J Gastroenterol 2012; 18: 4427–4434.

Disclosure of Interest: None declared

P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE COHORT STUDY

F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4, B. Sean2

1Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, 2Intensive Care, 3Transplantation, University of Alberta, Edmonton, Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease (MELD) score ≥40 have high risk of death without liver transplant (LT). This study aimed to evaluate these patients’ outcomes after transplant.

AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic patients who underwent LT at one Canadian center between 2002 and 2012. Primary exposure was severity of end-stage liver disease measured by MELD score at transplant (≥40 vs. <40). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival rates.

RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score ≥40. These patients had longer first ICU stay after LT (14 vs. 2 days; p <0.001). MELD score ≥40 at transplant was independently associated with first ICU stay after transplant ≥10 days (OR, 3.21). These patients had longer first hospital stay after LT (45 vs. 18 days; p <0.001); however, there was no significant difference in the rate of ICU readmission (18% vs. 22%; p = 0.58) or re-transplant rate (4% vs. 4%; p = 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and 5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no significant difference in cumulative survival stratified by MELD score ≥40 vs. <40 at transplant (p = 0.59).

CONCLUSION: Cirrhotic patients with MELD score ≥40 at transplant utilize greater postoperative health resources; however, derive similar long-term survival benefit with LT.

REFERENCES

Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062.

Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation in patients achieving a model for end-stage liver disease score of 40 or higher. Transplantation 2013; 95: 507-512.

Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients. Crit Care 2010; 14: R117.

Disclosure of Interest: None declared

P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT STUDY

J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2, N. O'Connell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4

1Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust, Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI, University of Warwick, Coventry, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: There is a quest for biomarker discovery in liver disease especially to detect cirrhosis at an early stage. Current methods are invasive, more often requiring a liver biopsy to confirm the diagnosis. For patients with Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst generally helpful, is unable to confirm the presence of fibrosis particularly in the presence of fat within the liver which is inevitable in most cases with NASH.

The gut microbiome is altered in several gastrointestinal disorders, resulting in altered gut fermentation patterns, which we (and others) have been able to recognise by analysis of volatile organic compounds (VOC) in urine, breath and faeces1. The altered structure of the small intestinal mucosa and increased gut permeability (noted in liver disease), we hypothesised, would also change the microbiome, hence recognisable by its unique “fermentome” pattern, making NASH distinguishable from controls.

AIMS & METHODS: To determine if NASH results in an altered VOC pattern in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguishable from cirrhotics vs non-cirrhotics.

33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8 with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and 12 controls (normal synthetic liver function). Urine was collected and 10 ml aliquots were stored frozen in universal containers. For assay, the containers were first heated to 40 ± 0.1oC. The headspace (the air above the sample) was then pumped from the containers and analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used for initial statistical evaluation, with a re-classification using a “leave one out” for calculating sensitivity and specificity.

RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in these different groups of liver disease. The control group was significantly different to all of the other groups with a sensitivity of 100%. Of the disease groups, NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively with specificity of 80%. NAFLD however had sensitivity of 50% but specificity of 80%.

CONCLUSION: This pilot study suggests the IMS (FAIMS – technology) offers a novel non-invasive approach to separate not only NASH from controls but also those with established cirrhosis using urine. It offers the potential for early non-invasive tracking of NASH and its complications.

REFERENCES

1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Aliment Pharmacol Ther 2014; 39: 780-789.

Disclosure of Interest: None declared

P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES

N. Ding1,*

1Gastroenterology, St Vincent's Hospital, Melbourne, Australia

Contact E-mail Address:[email protected]

INTRODUCTION: Endoscopic screening for gastro-oesophageal varices (GOV) is currently recommended for all cirrhotic patients. Noninvasive methods for liver fibrosis assessment are identifying increasing numbers of patients with “cirrhosis-range” liver stiffness measurements (LSM), increasing the number of referrals for screening endoscopy. The identification of simple non-invasive markers for the presence/absence of large gastroesophageal varices (GOV) would be clinically useful. We evaluated the performance of liver stiffness measurement (LSM) ± platelet count to identify the presence of large GOV in patients with Child Pugh (CP) A cirrhosis.

AIMS & METHODS: Data were collected retrospectively. The presence of cirrhosis was defined by LSM > 13.6 kPa using elastography. We performed a database search for patients with LSM > 13.6 kPa who underwent screening gastroscopy (2010 – 2013). Only patients with compensated liver disease were included. Large GOV were defined by diameter > 5mm or the presence of high risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the combination of these factors to identify patients with large GOV. A training set of 71 patients was used, and results were validated using a second cohort of 201 patients from two independent centres.

RESULTS: The combination of LSM and Pl was more accurate for identifying CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs. 0.78 [0.66 – 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk score was 0.11 (Sens = 0.88, Spec = 0.77, PPV = 0.33, NPV = 0.98, accuracy = 78%). Results in the validation cohort confirmed the discriminatory power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically relevant cut-offs to improve the negative predictive value (NPV) for large GOV. The NPV for the combination of LSM < 25 kPa and Pl ≥ 100 and was 100% in both the training cohort and validation cohort. 82 (42%) of patients overall met this criteria.

CONCLUSION: The combination of LSM < 25 kPa and Pl ≥ 100 can be used to identify patients with compensated cirrhosis who do not have large GOV. These patients do not benefit from endoscopic screening, but could be followed with annual LSM and full blood count.

REFERENCES

1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 1997.

2. de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53: 762–768.

3. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144, 102–111.e1.

4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement using Fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164–170.

Disclosure of Interest: None declared

P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN LABEL STUDY DATA

C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1, E. Berni3, C.J. Currie1

1Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff, 2Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of cirrhosis. In recurrent, overt, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent episodes.

AIMS & METHODS: The aim of this study was to characterise the impact of the number of prior HE episodes on the risk of future HE episodes. A post-hoc analysis was carried out using data from 322 patients with a history of HE from a phase 3, open-label study evaluating the long-term safety and tolerability of rifaximin-α 550mg BID. All eligible patients had a Conn score of 0–2 at enrolment, and had either successfully participated in a previous HE study with rifaximin-α (RFHE3001), or they were new patients enrolled with ≥1 verifiable episode of HE within the preceding 12 months.

RESULTS: 319 of 322 patients (647 observations) aged ≥18 years had all the information required for analysis. Median duration of follow-up was 17 months (IQR 8.9–25.4). Stratifying patient observations by number of prior HE episodes and using the Kaplan Meier method the probability of being event free at year one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and 0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539 (0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for 'one', 'two', ‘three’ and ‘four or more' prior HE episodes, respectively. Plotting the Kaplan Meier curves of time to next HE episode, stratified by the number of prior HE episodes, a clear association between decreased time to next HE episode and increased number of prior episodes was seen. Using log-rank tests, there was no significant difference between the survival curves of one prior and two prior HE episodes (χ2 = 0 on 1 degree of freedom (d.f.), p = 0.899), however there were significant differences between survival curves of one prior or two prior episodes and greater numbers of prior episodes (χ2 = 72 on 3 d.f., p<0.001).

CONCLUSION: This study supports the current understanding of the natural history of end-stage encephalopathy; as the number of prior HE episodes increased, the risk of subsequent HE episodes increased.

Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other: Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni Consultancy for: Norgine, C. Currie Consultancy for: Norgine

P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION

P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1, J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on behalf of Vienna Hepatic Hemodynamic Lab

1Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

Contact E-mail Address:[email protected]

INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repeatable tool to assess liver fibrosis and portal hypertension (HVPG). Recently, new quality criteria for TE measurements have been proposed (Boursier et al. Hepatology 2013): very reliable: IQR/M <0.1; reliable: IQR 0.1–0.3, or IQR/M >0.3 if TE <7.1 kPa; poor reliable: IQR/M >0.3 if TE >7.1 kPa.

AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension. Therefore we retrospectively identified patients undergoing TE, HVPG measurement and liver biopsy within 3 months at our tertiary care center.

RESULTS: Among 278 patients (48.7±13.1 years, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R = 0.648 vs. R = 0.636) and HVPG (R = 0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively.

CONCLUSION: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

Disclosure of Interest: None declared

P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL ENDOSCOPY

S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernández-Sordo'1, J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1, I. N. Guha1

1Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham, UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical Catholic University of Chile, Santiago, Chile

INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD) remains the gold standard test to screen for oesophageal varices (OV) in patients with liver cirrhosis. However, it has many limitations in terms of costs, accessibility and tolerability. Hence, there is a need for less invasive and simple techniques to replace C-OGD in this setting.

AIMS & METHODS: We aimed to compare the accuracy and acceptability of a portable, disposable, office-based, unsedated transnasal video endoscope (EG Scan™ II) with C-OGD for the detection of OV.

This was a prospective diagnostic study. Consecutive adult patients with confirmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited to participate in this study. We excluded patients with recurrent epistaxis (more than once a week); nasal obstruction; disease of the nasal cavity; history of variceal bleeding or band ligation therapy in the past 12 weeks. All subjects underwent two procedures on the same day (EG Scan followed by C-OGD), performed by two different operators blinded to the findings of the other test. Patients completed validated tolerability (10-point visual analogue scale (VAS)) and adverse events questionnaires on day 0 and day 14.

The primary outcome measure was diagnostic accuracy of EG scan (performed by one operator) against C-OGD (reference standard). In addition, interobserver agreement of the EG scan was calculated using the kappa (k) statistic, by nine blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.

RESULTS: 50 patients were recruited to the study (mean age 59 years +/-11, 70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%) completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%), p = 0.882). OV prevalence was 48.9%.

Sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95% confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI 0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI 0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis of any size OV (K = 0.45, 95%CI 0.40-0.49) and medium/large OV (K = 0.47, 95%CI 0.42-0.52).

Patients reported better experience (mean VAS+/-standard deviation (SD)) and higher preference (percentage) with EG Scan compared to C-OGD at day 0 (7.8+/-2.2 vs. 6.8+/-3.0, p = 0.058; 76.5% vs. 23.5%, p<0.001, respectively) and day 14 (7.0+/-2.3 vs. 5.5+/-3.2, p = 0.0013; 77.8% vs. 22.2%, p<0.001, respectively). There was no association between procedure preference and sedation use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p = 0.106; day 14: OR 0.24, 95%CI 0.02-2.56, p = 0.238). 4 patients (8.5%) experienced minor self-limiting epistaxis. No serious adverse events occurred.

CONCLUSION: EG Scan was accurate for the diagnosis of any varices and clinically significant OV. Interobserver agreement was modest. More importantly, patients’ experience and preference remained significantly higher for EG Scan 14 days after procedures independent of sedation use.

Disclosure of Interest: S. Sami Financial support for research from: Intromedic Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared, R. Mansilla-Vivar: None declared, J. Fernández-Sordo': None declared, J. White: None declared, A. Khanna: None declared, M. Coletta: None declared, S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial support for research from: Intromedic Ltd, Seoul, South Korea and Olympus Keymed UK., I. N. Guha: None declared

P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE

S.H. Shin1,*, B.K. Kim1

1Department of Internal Medicine, Institue of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea, Republic Of

Contact E-mail Address:[email protected]e

INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs and (2) small EVs with red sign or decompensated cirrhosis) are currently recommended for all cirrhotic patients. Recently, two new liver stiffness measurement (LSM)-based statistical equation models (PH risk score and Varices risk score) were introduced as a noninvasive, simple, accurate models for identifying presence of EVs and clinically significant portal hypertension [1].

AIMS & METHODS: We aimed to validate predictive value of the two models for detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.

Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis patients. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. LSM was measured by transient elastography; endoscopy was used as the standard for detection of EVs. PH risk score, Varices risk score and LSPS were calculated in all cases as follows: PH risk score = -5.953 + 0.188 x LSM + 1.583 x sex (1: male; 0: female) + 26.705 x spleen diameter/platelet count ratio, Varices risk score = -4.364 + 0.538 x spleen diameter – 0.049 x platelet count – 0.044 x LSM + 0.001 x (LSM x platelet count).

RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172 (25.5%) had HEVs. The area under the receiver-operating characteristic curve (AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950 (95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other factors: Varices risk score (0.907, 95% CI 0.876-0.939, p<0.001), LSM alone (0.873, 95% CI 0.842-0.904, p<0.001). At PH risk score < 4.0, 94.6% negative predictive value (NPV) was provided (481 patients), whereas 94.3% positive predictive value (PPV) was achieved (70 patients) at PH risk score > 10.0. In the same way, at Varices risk score < -2.5, 95.6% NPV was provided (413 patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score > 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients (81.6%) and 485 patients (71.9%), respectively.

CONCLUSION: The PH risk score is a reliable, noninvasive predictive model for detection of HEVs. Furthermore, the LSPS is considered as more simply applicable model having similar predictive value. Patients with PH risk score < 4.0 may avoid endoscopy safely, whereas those with > 10.0 should be considered for appropriate prophylactic treatments.

REFERENCES

1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144: 102-111.e101.

2. Kim BK, Han KH, Park JY, et al. A liver stiffness measurement-based, noninvasive prediction model for high-risk esophageal varices in B-viral liver cirrhosis. Am J Gastroenterol 2010; 105(6): 1382-1390.

Disclosure of Interest: None declared

P0044 PLALA SCORE PREDICT CIRRHOSIS PATIENT IN NONALCOHOLIC FATTY LIVER DISEASE

T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on behalf of JSG-NAFLD

1gastroenterology and hepatology, Yokohama city university, yokohama, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic and progressive liver injury in many countries1). NAFLD includes a wide spectrum of liver diseases that range from simple steatosis, which is generally a nonprogressive condition, to nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC), despite the absence of significant alcohol consumption. If NAFLD patients have liver cirrhosis, they need to be kept under surveillance for early detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in patients with NAFLD2). However, ad the number of NAFLD patients has reached 80–100 million in the United States and about 10 million NAFLD patients are estimated in Japan, it is virtually impossible to enforce in all patients.

AIMS & METHODS: To develop a mass screening system for general physicians, which can be used for predicting liver cirrhosis in NAFLD patients, using routine laboratory parameters.

A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD.

RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were selected as independent variables associated with cirrhosis in NAFLD patients by multiple logistic regression analysis. The optimal cutoff value of platelet count, serum albumin, and AST/ALT ratio was set at <15.3 104/μl (sensitivity; 81.6% specificity; 88.6%), <4.0 g/dl (sensitivity; 84.2% specificity; 84.6%), and >0.9 (sensitivity; 78.9%, specificity; 82.0%), respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AST/ALT ratio = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA ≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sensitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive predictive value).

CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

REFERENCES

1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.

2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362.

Disclosure of Interest: None declared

P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE RETROSPECTIVE STUDY

U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1

1Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre, Denmark

Contact E-mail Address:[email protected]

INTRODUCTION: Carvedilol may have a greater effect on portal and systemic hypertension than propranolol although reports are conflicting 1, 2. The impact of carvedilol versus non-specific betablockers (NSBB) on mortality on patients with cirrhosis remains to be evaluated.

AIMS & METHODS: We wanted to compare the impact on mortality of carvedilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic cirrhosis from the Danish National Patient Register during the period 1995 through 2010. We used the anatomical therapeutic chemical (ATC) classification to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk time as the time from the first prescription of either carvedilol or NSBB until death or end of follow-up (December 31, 2010). We adjusted for gender, age, heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of diuretics. We used univariate and multivariate Cox proportional hazard models to assess the HR. Persons with missing data were excluded from the analyses (0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC, USA).

RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol and NSBB, respectively. Three patients had received both carvedilol and NSBB and were excluded. Patients from the carvedilol group were mainly classified with uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we only included patients with uncomplicated cirrhosis in our mortality analysis (80 versus 1.857 patients). Significantly fewer patients in the carvedilol group died during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square p<0.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45 (95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7). The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs. 14%) prior to cohort entry were un-evenly distributed between users of carvedilol and NSBB. We did a sub-analysis where we matched patients on the presence of heart disease and variceal prior to cohort entry. In this sub-analysis we compared 80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found an adjusted HR of 0.38 (95% CI 0.2-0.7).

CONCLUSION: The use of carvedilol compared with NSBB in patients with cirrhosis was associated with lower mortality in this retrospective study.

REFERENCES

1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study. Dig Liver Dis 2014; 46: 251-256.

2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 2002; 36: 1367-1373.

Disclosure of Interest: None declared

P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD COMPONENT USE IN CIRRHOSIS

V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2, A. Burroughs3

1Nuffield Department of Medicine, University of Oxford, 2NHS Blood and Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom

INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both for prophylaxis and for treatment of bleeding, although indications and patterns of blood use are poorly characterised.

AIMS & METHODS: All NHS trusts with representation on the British Society of Gastroenterology membership list were invited to take part in a national audit. Data were collected prospectively on consecutive admissions with a confirmed diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/death/day 28. Specific information was requested on use of blood components, including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate.

RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years, 65% male) were collected from 85 hospitals. The predominant aetiology was alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all admissions were transfused a blood component; in 61% (238/391) this was for treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238) received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238) cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold was >8g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis the majority (61%, 94/153) received transfusion in the absence of a planned procedure. In patients transfused for prophylaxis prior to a procedure (59/153): 19% (3/16) received FFP at an INR ≤1.5 for high risk procedures and 33% (6/18) received FFP at an INR≤2 for low risk procedures; 36% (9/25) received platelet transfusion at a platelet count>50 prior to a procedure. The most frequent procedures resulting in prophylactic transfusion were paracentesis (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the most frequent cause of death.

CONCLUSION: Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component use is required, particularly in the group transfused for prophylaxis of bleeding. Further work is needed to improve patterns of blood use in cirrhosis to ensure patients are not exposed to unnecessary transfusion and its attendant harms.

Disclosure of Interest: None declared

P0047 SVR12 OF 99% ACHIEVED WITH A RIBAVIRIN-FREE REGIMEN OF ABT-450/R/OMBITASVIR AND DASABUVIR IN HCV GENOTYPE 1B-INFECTED PATIENTS

A. Maieron1,*, M. Puoti2, J. V. Enejosa3, P. Andreone4, Z. Ben Ari5, G. Norkrans6, M. Romero-Gomez7, W. Xie3, D.E. Cohen3, T. Podsadecki3

1Elisabeth Hospital, Linz, Austria, 2A. O. Ospedale Niguarda Ca Granda, Milan, Italy, 3AbbVie Inc., North Chicago, United States, 4University of Bologna, Bologna, Italy, 5The Chaim Sheba Medical Center, Tel Hashomer, Israel, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Hospital Universitario Nuestra Senora De Valme, Seville, Spain

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor (identified by AbbVie and Enanta) dosed with ritonavir (r). Ombitasvir (formerly ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is a non-nucleoside NS5B RNA polymerase inhibitor. We report the sustained virologic response 12 weeks post-treatment (SVR12) achieved in HCV genotype 1b-infected patients after treatment with these 3 direct-acting antivirals (3D regimen) with or without ribavirin (RBV).

AIMS & METHODS: Five hundred ninety-nine treatment-naïve and prior pegIFN/RBV-experienced HCV genotype 1b-infected patients without cirrhosis were enrolled and received study drugs in the PEARL-II and PEARL-III randomized phase 3 studies. Patients were randomized 1:1 to co-formulated ABT-450/r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice daily) with or without weight-based RBV (1000 – 1200 mg daily).

RESULTS: The combined SVR12 rate from PEARL-II and PEARL-III was 99.3% in 301 patients who received 3D regimen without RBV vs. 98.7% in 298 patients who received 3D + RBV. Two patients (0.7%) receiving 3D without RBV did not achieve SVR12, both due to missing week 12 post-treatment follow-up. Four 3D + RBV patients did not achieve SVR12: 1 (0.3%) due to virologic breakthrough, 1 (0.3%) due to missing SVR12 data, and 2 (0.7%) due to study drug discontinuation for adverse events. SVR12 rates did not differ between 3D and 3D + RBV by baseline factors including IL28B genotype, sex, age, race, ethnicity, BMI, fibrosis stage, and HCV RNA viral load. No patients receiving 3D and 0.7% of patients receiving 3D + RBV discontinued due to adverse events.

SVR12 by baseline factors, n/N (%)3D3D + RBV
Overall299/301 (99.3)294/298 (98.7)
Treatment-naïve208/210 (99.0)209/210 (99.5)
PegIFN/RBV Treatment-experienced91/91 (100)85/88 (96.6)
IL28B non-CC genotype249/250 (99.6)240/244 (98.4)
Female160/160 (100)147/149 (98.7)
Age ≥6534/34 (100)29/29 (100)
Black race16/16 (100)13/13 (100)
BMI ≥ 30 kg/m262/64 (96.9)44/45 (97.8)
Fibrosis stage, F331/33 (93.9)33/34 (97.1)

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CONCLUSION: Irrespective of previous pegIFN/RBV treatment response and other baseline factors, HCV genotype 1b-infected patients achieved high SVR rates after 12 weeks of 3D without RBV. Overall, only 1 (3D + RBV) of 599 (0.2%) patients experienced virologic breakthrough and none experienced relapse. Both regimens were well tolerated. ABT-450/r/ombitasvir and dasabuvir without RBV achieves optimal treatment efficacy in HCV genotype 1b-infected patients without cirrhosis.

Disclosure of Interest: A. Maieron Financial support for research from: Roche, MSD, Consultancy for: MSD, Janssen Therapeutics, AbbVie, Boehringer Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, M. Puoti: None declared, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, P. Andreone Financial support for research from: Roche, Merck, Gilead, Consultancy for: Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead, MSD, BMS, Z. Ben Ari Consultancy for: MSD, Janssen, AbbVie, Boehringer Ingelheim, BMS, GSK, G. Norkrans: None declared, M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, W. Xie Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: AbbVie

P0048 ADHERENCE TO PRESCRIBED DOSES OF ABT-450/R/OMBITASVIR, DASABUVIR, AND RIBAVIRIN IN THE PHASE 3 PEARL-II, PEARL-III, AND PEARL-IV TRIALS

D. Bernstein1, R. Marinho2,*, D. Cohen3, F. Bredeek4, F. Schneider5, G. Norkrans6, M. Curescu7, M. Bennett8, M. Maevskaya9, J. Fessel10, W. Xie3, Y. Luo3, J. Enejosa3

1Hofstra North Shore- LIJ School of Medicine, Manhasset, United States, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisbon, Portugal, 3AbbVie Inc., North Chicago, 4Metropolis Medical Group, San Francisco, United States, 5Markusovszky Hospital, Szombathely, Hungary, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Life Search SRL, Timisoara, Romania, 8Medical Associates Research Group, San Diego, United States, 9First Moscow State Medical Universita n.a. I. M. Sechenov, Moscow, Russian Federation, 10Kaiser Permanente, San Francisco, United States

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, dosed with ritonavir(r); ombitasvir(ABT-267) is an NS5A inhibitor; dasabuvir(ABT-333) is an NS5B RNA polymerase inhibitor. The phase 3 PEARL trials examined the efficacy and safety of all-oral, interferon-free, 12-week regimens of ABT-450/r/ombitasvir+dasabuvir(3D) with or without ribavirin(RBV) in HCV genotype(GT) 1a- and 1b-infected patients(pts). We report pt adherence to the regimens in these trials.

AIMS & METHODS: Pts were randomized to co-formulated ABT-450/r/ombitasvir(150mg/100mg/25mg QD)+dasabuvir(250mg BID) with either weight-based RBV or placebo (PBO)/no RBV. Adherence was calculated by pill counts as the percentage of capsules/tablets taken relative to the total capsules/tablets expected to be taken.

RESULTS: In each trial, mean pt adherence to every study drug was >98.5%(Table). Adherence was comparable in those who received 3D with RBV, 3D with PBO, or 3D alone. SVR12 rates were 96.6-100% in treatment-experienced and treatment-naïve HCV GT1b-infected pts receiving 3D+/-RBV. SVR12 rates were 97.0% and 90.2%, respectively, in treatment-naïve GT1a-infected pts receiving 3D+RBV or 3D+PBO. Only 1 GT1b-infected pt had virologic failure. Pts with virologic failure had adherence rates comparable to the overall rates, but the majority was GT1a-infected and did not receive RBV. Five pts had adherence rates<80% for one or more study drugs, none of whom had virologic failure. Among 401 pts receiving 3D with RBV and 509 pts receiving 3D without RBV, 2(0.5%) and 2(0.4%), respectively, discontinued study drug due to adverse events.

PEARL-II Treatment-experienced* GT1b
PEARL-III Treatment-naïve GT1b
PEARL-IV Treatment-naïve GT1a
3D+RBV3D3D+RBV3D+PBO3D+RBV3D+PBO
Adherence, Mean % (SD)
ABT-450/r/ ombitasvir99.7 (2.3) n = 87100.0 (2.6) n = 9299.8 (1.2) n = 205100.0 (1.1) n = 20599.7 (1.9) n = 9899.7 (3.3) n = 190
dasabuvir99.0(3.2) n = 9099.2 (1.6) n = 9499.8 (1.2) n = 20599.9 (1.1) n = 20599.2 (2.0) n = 9899.1 (3.6) n = 190
RBV99.1 (6.5) n = 87NA99.6 (2.1) n = 20599.6 (2.6) n = 20398.6 (3.2) n = 9098.7 (3.6) n = 181
SVR12, % (n/N)96.6 (85/88)100 (91/91)99.5 (209/210)99.0 (207/209)97.0 (97/100)90.2 (185/205)

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Adherence data for each capsule/tablet not available for all pts.

In PEARL-II, 7 randomized patients were excluded from the intent-to-treat efficacy population because they received non-coformulated ABT-450/r/ombitasvir (N = 6) or could not be genotyped (N = 1).

CONCLUSION: Participants in these phase 3 trials had excellent adherence (>98.5%) to doses of ABT-450/r/ombitasvir, dasabuvir, and RBV. Low adherence rates, while infrequent, were not associated with virologic failure.

Disclosure of Interest: D. Bernstein Financial support for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, R. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, D. Cohen Shareholder of: AbbVie, Other: AbbVie, F. Bredeek Financial support for research from: AbbVie, BMS, Gilead, Janssen, Merck, Sumagen, ViiV, Lecture fee(s) from: Merck, ViiV, Consultancy for: Merck, ViiV, F. Schneider: None declared, G. Norkrans: None declared, M. Curescu: None declared, M. Bennett Shareholder of: AbbVie, M. Maevskaya: None declared, J. Fessel: None declared, W. Xie Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie

P0049 ASSOCIATION BETWEEN TLR-3 GENE POLYMORPHISM RS3775291 AND PROGRESSION OF HEPATITIS C VIRUS INFECTION

F.-Z. Fakhir1,2,*, M. LKHIDER1

1Faculté des Sciences, Chouaib Doukkali University, El Jadida, 2Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatitis C virus (HCV) is a major global health problem with about 210 million people infected worldwide, and constitutes the most important cause of chronic liver disease. HCV is an enveloped positive-strand RNA virus belonging to the genus Hepacivirus of the family Flaviviridae. During the viral replication cycle, double-stranded RNA (dsRNA), produced as an intermediate, is sensed by several pattern recognition receptors (PRRs) of the innate immune system including Toll-like receptors (TLR). TLRs constitute a family of receptors playing a key role in innate and adaptive immune response, among them TLR3,-7 and -8, which are expressed on endosomal membrane, and have been suggested to play an important role in antiviral immune responses based on their recognition of dsRNA and single-stranded RNA (ssRNA). Single nucleotide polymorphisms (SNPs) may shift balance between pro- and anti-inflammatory cytokines, contributing to successful resistance to infection or leading to chronic inflammation and cancer. The aim of this study was to investigate the association between the TLR-3, -7 and -8 polymorphism and the outcome of HCV infection.

AIMS & METHODS: 517 patients were enrolled in the study and genotyped for the TLR3, -7 and -8 SNPs. Logistic regression was used to assess the association between the polymorphisms and the outcome of the infection.

RESULTS: A significant association between TLR-3 SNP at rs3775291 and risk of advanced liver disease was identified. The rs3775291-A/A genotype was more common in subjects with advanced liver disease than subjects with mild chronic hepatitis C (OR = 3.81; 95% CI, 2.16-6.72; p = 0.000004) and this difference was higher with healthy controls (OR = 5.34; 95% CI, 2.70-10.58; p = 0.000002).

CONCLUSION: Our findings indicate that a TLR-3 SNP rs3775291 is associated with progression of HCV infection to cirrhosis and hepatocellular carcinoma.

Disclosure of Interest: None declared

P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS

M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4, F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J. V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10

1Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital Germans TríasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and Southern California Research Center, Coronado, 7University of Pennsylvania, Philadelphia, 8The Queen’s Medical Center – Liver Center, Honolulu, 9AbbVie Inc., North Chicago, United States, 10University of Milan, Milan, Italy

INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition. We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) (3D regimen) with or without RBV.

AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials (PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of RBV to the safety and efficacy of the 3D regimen, were used to evaluate the incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia, jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were assessed at baseline and every 1-2 weeks per protocol.

RESULTS: Total bilirubin elevations of >3X ULN occurred in 23/401 (5.7%) 3D+RBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regimen. The majority of patients in each group (>90%) had normal total bilirubin levels at the end of treatment. Mean total bilirubin levels were significantly higher at each treatment visit in the RBV-containing treatment groups. Mean total bilirubin peaked at week 1 in both treatment groups (predominantly indirect), and declined to baseline by week 2 in the RBV-free group. Events of hyperbilirubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of treatment and did not result in study drug discontinuation. One patient underwent RBV dose modification and one interrupted study drug due to hyperbilirubinaemia; both patients achieved sustained virologic response 12 weeks post-treatment. Two patients receiving 3D+RBV experienced ALT ≥3X ULN and total bilirubin ≥2X ULN, however, the timing and predominance of indirect bilirubin were not consistent with drug induced liver injury. No serious adverse events related to hyperbilirubinaemia were reported.

Bilirubin-related events, n (%)3D+RBV (N = 401)3D (N = 509)
Any bilirubin-related event21 (5.2)4 (0.8)
Hyperbilirubinaemia13 (3.2)3 (0.6)
Jaundice11 (2.7)1 (0.2)
Total bilirubin >3X ULN23 (5.7)2 (0.4)

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CONCLUSION: Low rates of hyperbilirubinaemia were observed with both 3D regiments but was less frequent in the RBV-free 3D regimens, suggesting that increases in bilirubin associated with ABT-450-containing regimens are enhanced by RBV-induced haemolysis. Bilrubin-related adverse events were infrequent with both regimens and did not affect treatment response.

Disclosure of Interest: M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, R. T. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, R. Planas Vila Financial support for research from: Roche, MSD, BMS, Gilead, Janssen, Lecture fee(s) from: Roche, MSD, BMS, Gilead, Janssen, Boehringer Ingelheim, Consultancy for: Roche, MSD, BMS, Gilead, Janssen, D. Bernstein Financial support for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, F. Rodriguez-Perez Lecture fee(s) from: BMS, Merck, Consultancy for: AbbVie, Gilead, Janssen, Merck, T. Hassanein Financial support for research from: AbbVie, Boehringer-Ingelheim, BMS, Eisai, Gilead, Janssen, Idenix, Ikaria, Mochida, Takeda, Mochida, Roche, Ocera, Sundise, Salix, Taigen, Takeda, Vertex, Lecture fee(s) from: BMS, Genentech, Gilead, Salix, Consultancy for: AbbVie, BMS, K. R. Reddy Financial support for research from: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Genfit, Consultancy for: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Idenix, N. Tsai Financial support for research from: AbbVie, Janssen, Genentech-Roche, Vertex, BMS, Lecture fee(s) from: Gilead, Genentech-Roche, BMS, Vertex, Merck, Janssen, Consultancy for: AbbVie, Gilead, Janssen, S. Lovell Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, M. Colombo Financial support for research from: Merck, Roche, BMS, Gilead, Lecture fee(s) from: Tibotec, Roche, Novartis, Bayer, BMS, Gilead Sciences, Vertex, Consultancy for: AbbVie, Merck, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, Abbott, Boehringer Ingelheim, GSK, GenSpera

P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS INDEPENDENT OF PATIENT SUBGROUPS

M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5, E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7

1Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital, Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel, Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San Diego Digestive Diseases, San Diego, 6Texas Liver Institute, University of Texas Health Science Center, San Antonio, 7AbbVie, North Chicago, United States

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta; ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a non-nucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral (3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected patients, 96.3% of treatment-naïve patients (SAPPHIRE-I trial) and 96.2% of pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV RNA <25 IU/mL at post-treatment week 12).

AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were randomized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir (150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV (1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the two trials were pooled, and SVR12 rates were calculated overall and according to race, ethnicity, and region.

RESULTS:

Источник: [https://torrent-igruha.org/3551-portal.html]

PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen - something

REPAIR MANUAL - Euromachines

REPAIRMANUAL

NEW HOLLAND

VL570 VM370

VL610 VM460

VL620

VL630

VL640

VL660


SPECIFICATIONS

Chapter 1

CONTENT

Section Description Page

identification 3

..........................................................

Machine

4

...................................................................

Dimensions

machine technical specifications 6

...................................

Self--propelled

equipment technical specifications 9

.....................................

Harvesting

604 82 321 00 -02 - 2005


2 SPECIFICATIONS

604 82 321 00 -02- 2005


SPECIFICATIONS 3

MACHINE IDENTIFICATION DATA

Model Type Serial number Machine number

VL 660 664 001 001

VL 640 660 001 001

VL 630 660 001 001

VL 620 656 001 001

VL 610 656 001 001

VM 460 636 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

657 001 001

637 001 001

VL 570 655 001 001

VM 370 633 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

A = Manufacturer’s label

B = Stamped frame number

VL 610 ÷ 660 and VM 460: 604801000 (GB)

VL 570 and VM 370: 604801300 (GB)

Reference:

654 001 001

634 001 001

OPERATOR’S MANUAL

SPARE PART CATALOGUE

604 82 321 00 -02 - 2005


4 SPECIFICATIONS

604 82 321 00 -02- 2005

2100 litres

2600 litres

3200 litres


SPECIFICATIONS 5

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Code DIMENSIONS (mm)

H1 Height: without cab

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3810 3810

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 2000 to 2600

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 2600 l

HB5 Height under clearance hoppers, 3200 l

E Wheelbase 2860

La1 Max. width at the hoppers hoppers, 2100 l 2500/2300

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

2100 l + cab 3000/2800

2600 l or 3200 l 3000

self--propelled

Only

machine

self--propelled

Only

machine

2590 2390

2830 2630

LaB1 Hopper width 2100 l 2500 2300

2600 l

LaB2

l 3200

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 + Gb = La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 28

420/85

Tyres

R 28

480/70

Tyres

R 28

540/65

to front wheels Tyres

next

R 24

420/70

3000

3000

2800

2160 + 454 = 2614 1790 + 454 = 2244

2260 + 480 = 2740 1860 + 480 = 2340

2340 + 540 = 2880

Tyres 600x55x30.5 2360 + 600 = 2960

1930 + 420 = 2350 1730 + 420 = 2150

(V2 + Gb = La AV) Tyres 13.6 R 24 1930 + 350 = 2280 1730 + 350 = 2150

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

without cab 5390

with cab 5500 (5650)

DAV1 Front offset: without cab 910

DAV2 with cab 1050

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

604 82 321 00 -02 - 2005


6 SPECIFICATIONS

604 82 321 00 -02- 2005

1800 litres

2400 litres or 2200 litres


SPECIFICATIONS 7

COMMERCIAL DESCRIPTION VL 570 VM 370

Code DIMENSIONS (mm)

H1 Height: without cab 3160 3040

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3600 3420

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 1800 to 2300 from 1950 to 2450

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 1800 l

HB5 Height under clearance hoppers, 2400 l

E Wheelbase 2730

La1 Max. width at the hoppers hoppers, 2400 l

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

l + cab

2400 l +cab

2400

self--propelled

Only

machine

self--propelled

Only

machine

2540 2340

2750 2540

LaB1 Hopper width 1800 l 2500 2300

2200 l

LaB2

l 2800

2400

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 +Gb=La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 24

420/70

Tyres

R 24

480/65

Tyres

R 24

460/70

Tyres

R 24

340/85

Tyres 11.2R24

to front wheels Tyres

next

R 20

280/70

+ Gb = La AV) Tyres

(V2

R 20

320/70

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

DAV1 Front offset: without cab

DAV2 with cab

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

2065 + 431 = 2496

2095 + 484 = 2579

2095 + 462 = 2557

2800

1975 + 366 = 2341 1775 + 366 = 2141

1755 + 291 = 2046

1694 + 275 = 1969

1942 + 315 = 2257 1742 + 315 = 2057

without cab 4910 (5110)

with cab 4980 (5180)

604 82 321 00 -02 - 2005


8 SPECIFICATIONS

WEIGHT

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

PTAC Total allowed weight under load (kg) 9500

Partition front axle (kg)

rear axle (kg)

4200

5300

weight with harvest- Total 8700 (9200)

Empty weight with harvest Total 8700 (9200)

Empty

equipment and without

g q p ing

(with) destemmers

Weight of one wheel (kg) 420/70 R 24

Thermal engine weight (kg)

FEEDING/EXHAUST

480/70 R 28

540/65 R 28

Fuel tank Used fuel

Capacity (litres)

Diesel oil

Engine feeding system Direct injection

Air filter Make

Type

Engine cooling Water capacity (litres)

250

DONALDSON

ELB 12--0265

Fan Sucking

Cooling fan ∅ (mm) 610 584

DRIVE

Pump for engine fan Make

Displacement (cm�/rev.)

Empty operating speed

(rpm)

Capacity (l/minute), output

0.9

Fan motor Make

Variable flow inching hy-

draulic pump:

Displacement (cm�/rev.)

Make

Type

Total displacement

(cm�/rev.)

SAUER

17

(1.02 x engine speed)

35

SAUER

12.2

REXROTH

A4VG

from 0 to 105


DRIVE (follows)

SPECIFICATIONS 9

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Priming pump Displacement (cm�/rev.)

Capacity (l/minute), output

0.9

Front wheel motor Make

Type

Rear wheel motor Make

Displacement (cm�/rev.)

Type

Displacement (cm�/rev.)

26

57.3

POCLAIN

MS 08

1043

POCLAIN

MSE 18

2636 (1406/1230)

Max. speed (km/h) in road position 25 km/h

Max. speed (km/h) in field position 12

Hydraulic oil

Capacity l/minute

Oil type

Extractor pump and con-

veyors

Shaking

pump

Steering/lifting/hopper pump

Total

Reservoir 65

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

NEW HOLLAND: Hydrosystem 68

Hydrosystem 68 BIO S

REXROTH

”Load sensing” from 0 to 45

2500 (see engine speed)

101.2

SAUER

22

2500 (see engine speed)

50

SAUER

14

(1.02 x engine speed)

STEERING Hydrostatic

Type EATON QAMP 146 cm�/rev.

BRAKING

Service brake Supplied by the hydrostatic transmission

Parking brake (acting on the two rear wheels) Operated by ONE pedal and by the steering

Parking brake Operated by left manual lever

29

604 82 321 00 -02 - 2005


10 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

TILTING CORRECTION 30%

PLATFORM CAB

Heated and air--conditioned cab Depending on the model

Activated charcoal filter Option

On--board computer �

Grand--Luxe seat

Pneumatic seat �

Multi--function lever �

LIGHTING AND WARNING LIGHTS

High/low beams 2

Front parking lights 2

Rear parking lights 2

Direction indicator warning lights Front

Rear

Side

Stop lights 2

License plate light 1

Reflector Rear 2

Revolving beacon with cab 2

Supply voltage / battery 12 V / 180 Ah

Alternator 120 A

2

2

2


HARVESTING EQUIPMENT

HARVESTING HEADER

SPECIFICATIONS 11

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Type Swinging, self--aligning

System Shaking, SDC

Number of shakers 14

Straight/elbow connecting rod 13/1

Shaking drive Motor manufacturer

Displacement (cm�/rev.)

ECU:

Ratio

Toe--in adjustable from the operator’s seat

Grease: TUTELA MRM2

SAUER

Amplitude settings 4

22

4/1

2.7 kg

Min. clearance under the frame (mm) 2000

Grape harvesting useful height (mm) 1650

Harvesting tunnel width (mm) 500

604 82 321 00 -02 - 2005


12 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

RECEIVING/TRANSPORTATION

Noria system Buckets per chain

Type

Synchronized

63/61

XXL/small

in field speed

Width of flexible stock guides (mm) from195to265

Tightness length (mm) 2100

Harvesting min. height (mm) 150

Drive Motor manufacturer

Harvesting conveyors Width (mm)

Displacement (cm�/rev.)

Max. operating speed rpm

Reverse

Single operation Motor manufacturer

Displacement (cm�/rev.)

EATON

500

600

about 750

yes

EATON

31.6


CLEANING

SPECIFICATIONS 13

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

2 upper extractors with removable

stalk choppers

2 lower extractors with

2 independent stalk choppers, en-

abled by shaking

HOPPERS

Diameter (mm)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Diameter

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Direction of rotation

460

hydraulic

SAUER

11

430

Hydraulic system

SAUER

6

Hydraulic system

EATON

8.2

reverse to the wheels

Capacity 2 x 1600

2 x 1300

2 x 1050

Electrically--operated distribution auger Control independent of the grape harvester

604 82 321 00 -02 - 2005


14 SPECIFICATIONS

604 82 321 00 -02- 2005


WEIGHT

SPECIFICATIONS 15

COMMERCIAL DESCRIPTION VL 570 VM 370

PTAC Total allowed weight under load (kg)

Partition front axle (kg)

Empty weight with

harvesting equipment

and without (with)

destemmers

Weight of one wheel

(kg)

rear axle (kg)

Total

Thermal engine weight (kg)

FEEDING/EXHAUST

Fuel tank Capacity 160 litres * *

4--cylinder engine --

-- ISO power (KW/CV)

-- Displacement = 1125 cm 3 /cylinder

Air filter Make

Type

Engine cooling Liquid capacity (litres)

Fan

94/128

Air/air intercooler * *

DRIVE

Variable displace-

ment inching hy-

draulic pump:

”Rexroth” A4VG90

Displacement elimin-

ation:

Drive:

Total displacement

90 cm�/rev.

*

*

electr.

*

94/128

*

*

electr.

*

604 82 321 00 -02 - 2005


16 SPECIFICATIONS

DRIVE (follows)

COMMERCIAL DESCRIPTION VL 570 VM 370

Priming pump Displacement 25 cm�/rev.

604 82 321 00 -02- 2005

Capacity (l/minute), output

0.9

Front wheel motor Make ”Poclain”

Type MSE 05

Displacement 688 cm�/rev.

Rear wheel motor Make ”Poclain”

Type MSE 11

Displacement 843/843

cm�/rev.

* *

Double steering valve * *

Front drive wheels in road position * *

”Twin lock” antiskid * *

Torque reduction on front wheels, optional * *

Max. speed in road position, 25 km/h * *

Max. speed in field position, 12 km/h * *

Hydraulic oil

Capacity l/minute

Oil type

Total

Reservoir, 65 litres

New Holland

Hydrosystem 68

Hydraulic filtering (intake/return) * *

Extractor pump and

conveyors

Shaking

pump

Make ”Sauer”

Displacement 44 cm�/rev.

Idle operating rpm speed =

engine

Capacity (l/minute), output

0.9

Make ”Sauer”, double

Displacement 22 cm�/rev.

Idle operation rpm speed =

93% of engine speed

Capacity (l/minute), output

0.9

*

*

*

*

*

*

*

*

*

*

*

*


SPECIFICATIONS 17

COMMERCIAL DESCRIPTION VL 570 VM 370

Steering/lifting/hopper

pump

STEERING

Make ”Sauer”, double

Displacement 11 cm�/rev.

Idle operation rpm speed

= 93% of engine speed

Capacity (l/minute), output

0.9

Type: ”Eaton” valve, 100 cm 3 /rev. * *

BRAKING

Hydrostatic service brake * *

Parking brake (acting on the two rear wheels) * *

Manually--operated parking brake, on the left * *

Electrically--operated independent brakes No No

*

*

604 82 321 00 -02 - 2005


18 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

TILTING CORRECTION

Max. tilting (%) 25 25

Max. tilting in road position (%) 8 8

Max. tilting in work position (%)

(with destemmers or special implement and

front wheels with ballasts)

FRAME

604 82 321 00 -02- 2005

32 32

Harvesting header quick uncoupling * *

Link fitting possibility * *

Front and rear tracks = see relevant SB * *

PLATFORM CAB

Heated and air--conditioned cab

Activated charcoal filter

ELTEC control panel * *

Imitation leather seat as standard outfit * *

Pneumatic seat, with cab, optional * *

Multifunction lever, number of push buttons 18 18

Electrical inching control, adjusted through

sensors (optional radar)

Electrical presetting for:

-- electrically--operated rear view mirrors

-- CDHA

-- rear viewing

* *

*

*

*

*

*

*


SPECIFICATIONS 19

COMMERCIAL DESCRIPTION VL 570 VM 370

LIGHTING AND WARNING LIGHTS

High/low beams

Front parking lights

Rear parking lights

Direction indicator

warning lights

Stop lights

License plate light

Front

Rear

Side

Reflector Rear

Revolving beacons

Battery, capacity (AH) 135 135

Alternator -- 120 A * *

604 82 321 00 -02 - 2005


20 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

HARVESTING EQUIPMENT

HARVESTING HEADER

Harvesting header hour counter yes yes

Type -- swinging, self--aligning * *

SDC shaking system * *

Number of shakers 14 12

Straight/elbow flexible connecting rod 13/1 11/1

Shaking drive ”Sauer/Eaton” motor

Toe--in adjustable

from the operator’s

seat

604 82 321 00 -02- 2005

Displacement

(cm�/rev.)

Reducer control unit:

1/4

Grease: GR75MD

22

*

22

* *

Amplitude settings 3 3

Removable shakers, optional * *

Min. clearance under the frame

1950/2450 mm

Min. clearance under the frame

1800/2300 mm

Grape harvesting useful height (mm) 1050 900

Harvesting tunnel

width (mm)

RECEIVING/TRANSPORTATION

Noria system Large buckets

Small buckets

Fastening by 2 plates

Drive gears:

16/59

17/58

Width of flexible stock guides (mm) 195/265 165/235

Tightness length 1750 mm * *

Min. harvesting height 150 mm * *

Operation ”Eaton” motor

Displacement 395

cm�/rev.

*

55

*

*

*

*

53

* *

*


SPECIFICATIONS 21

COMMERCIAL DESCRIPTION VL 570 VM 370

Harvesting con-

veyors

Width 450 mm

Max. operating speed

rpm

Reverse

Single operation ”Eaton” motor

CLEANING

2 upper extractors

with removable

stalk choppers

2 lower extractors

(optional)

2 independent stalk

choppers, enabled

by noria in propor-

tional

HOPPERS

Capacity

Displacement 31.6

cm�/rev.

Diameter 430 mm

”Sauer” motor

Displacement 11

cm�/rev.

Electrically--operated

speed

Diameter 430 mm

”Sauer” motor

Displacement

6cm�/rev.

Electrically--operated

speed

”Eaton” motor

Displacement

8.2 cm�/rev.

*

*

* *

1800 litres *

2360 litres *

Distribution auger

”Eaton” motor

Displacement

31.6 cm�/rev.

Adjustable speed

*

*

*

*

*

*

*

* *

*

*

*

*

*

604 82 321 00 -02 - 2005


22 SPECIFICATIONS

604 82 321 00 -02- 2005


Section Description

00 Maintenance

REPAIRMANUAL

CONTENT

05 Machine preparation and equipment

10 Engine

14 Live PTO

29 Hydrostatic transmission

33 Brakes & Controls

35 Hydraulic systems

36 Pneumatic systems

37 Towing hooks and ballasting

39 Frames

41 Steering

44 Wheels

50 Cab climate control

55 Electrical systems

58 Attachments/headers

60 Product feeding

74 Cleaning

80 Grape storage -- hoppers

88 Accessories

90 Platform, cab, bodywork and decals

1

604 82 321 00 -02 - 2005


2

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 1

SECTION 00 - MAINTENANCE

Chapter 1

CONTENT

Description Page

......................................................

Section

Capacities 2

....................................................................

00.000

engine maintenance 3

...................................................

Thermal

5

.....................................................................

Greasing

filter 8

................................................................

Hydraulic

9

.....................................................................

Washing

system maintenance 13

.................................................

Hydraulic

maintenance and winter storage 15

........................................

Routine

604 82 321 00 -02 - 2005


2 SECTION 00 - MAINTENANCE - CHAPTER 1

Item to be serviced

Self--propelled machine

greasers

604 82 321 00 -02- 2005

CAPACITIES

LUBRICANTS AND FLUIDS

Quantity

dm3 (litres)

Recommended

product

Grease

AMBRA GR 9

International

classification

Lithium--calcium based grease,

consistency NLGI 2

Harvesting machine greasers Grease 24 cartridges

Noria ECU 1 Food type re. 62777339

Shaking rear connecting rod

articulations

Shaking ECU 2.7 kg GR 75 MD

Engine sump and filter/s

6--cylinder engine

4--cylinder engine

15

9.5

Grease Teflon silicone grease

NH 720 A

Oil

AMBRA SUPER GOLD

HSP

15W - 40

Reservoir 65 Oil

AMBRA

HYDROSYSTEM 68

Cooling system 20 AMBRA

AGRIFLU (50%) +

Clean water (50%)

Sitef degree 3

410--g cartridge, re. 920019780

Re.: 661874

molybdenum bisulfide grease,

consistency NLGI 2

SAE 15W40

API CH -- 4

ACEA E3/E5

ISO 68

DIN 51524 -- part 2


a) After the first 50 hours

SECTION 00 - MAINTENANCE - CHAPTER 1 3

-- Let the engine run until it reaches the stan-

dard operating temperature.

-- Replace the diesel oil filter cartridge/s.

-- Check alternator and compressor belt ten-

sion.

-- Check engine tightness.

b) Every day or every ten hours, check:

-- the oil level,

-- the coolant level,

-- the radiator core cleanliness.

THERMAL ENGINE MAINTENANCE

c) Every 400 hours, or before each harvest-

ing season, replace:

-- the engine oil;

-- the oil filter cartridge/s;

-- the diesel oil filter cartridge/s;

-- Check belt tension.

-- Check the radiator core cleanliness.

-- If the air filter clogging indicator comes on,

clean the main cartridge by compressed

air, blowing inside out.

Be careful not to use a pressure over

6 bar; shift the nozzle downwards and hold

it at about 3 cm from the paper.

d) Only before each harvesting season:

-- replace the air filter main cartridge.

NOTE: the diesel oil filter cartridges should be re-

placed more often if the diesel oil conditions require

it.

604 82 321 00 -02 - 2005


4 SECTION 00 - MAINTENANCE - CHAPTER 1

14

20

13

19

10

E

F

604 82 321 00 -02- 2005

18

11

12

16

A B

1 2 3 4 5 6 7 8

17

15

10 11 12

19 20

9

13 14 15 16 17 18

D

C

1 2 3 4 5 6 7

8 9 10 11 12 13

14 15 16 17 18 19 20

4

6

2

8

1

3

5

7

VM 460

9

VL 610 ÷ 660


SECTION 00 - MAINTENANCE - CHAPTER 1 5

GREASING POINT POSITION - VL 610 ÷ 660 and VM 460

The greasing ramp is located on the harvesting

equipment central gangway. All these points must

be greased with food--type grease every day, after

washing.

A) Noria drive shaft

B) Shaking control shaft

C) Right shaking control connecting rod

D) Left shaking control connecting rod

E) Right shaking plate

F) Left shaking plate

There is no centralized greasing on the self--pro-

pelled machine, thus you need to grease daily only

the following:

-- 2 x 3 greasers on the front legs

HARVESTING EQUIPMENT

These positions are not localised and should be

greased every 50 hours:

� 2 x 2 greasers on the hopper cylinder axes

� 2 x 1 greaser on the lower stalk choppers

TOTAL: 26

SELF -PROPELLED MACHINE

To grease every 50 hours:

� 2 x 1 greaser on the steering cylinder pivot

� 2 x 2 greasers on the steering bar pivots

� 2 greasers on steering relay

� 2 x 2 greasers on the wheel link pivot

� 2 x 2 greasers on the rear lifting cylinder

TOTAL: 16

604 82 321 00 -02 - 2005


6 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 7

GREASING POINTS FOR VL 570 and VM 370

Position and number of greasers Greasing frequency

SELF -PROPELLED MACHINE

Front legs 2 x 3 6

10 h 50 h

Steering cylinder articulation 2

Steering relays 2

Steering bar ball joints 4

Rear wheel link articulation 2 x 2 4

Rear lifting cylinder articulation 2 x 2 4

Total 22

HARVESTING EQUIPMENT

Shaking front plate 2 x 2 4

Shaking control link rods 2 x 2 4

Right side shaking shaft bearing 1 1

Left side noria shaft bearing 1 1

Belt bearings 2x4 8

Hopper tilting cylinder 2x1 2

Hopper articulation 2x1 2

Harvesting equipment rear articulation 1 1

Lower stalk chopper 2 x 1 2

Total 25

604 82 321 00 -02 - 2005


8 SECTION 00 - MAINTENANCE - CHAPTER 1

Hydraulic filter cover

During reassembly, pay attention to the assembly

direction:

-- the A side with only one arrow on the cover

must be directed towards the return line;

-- the B side with two arrows on the cover must

be directed towards intake lines.

604 82 321 00 -02- 2005

A

B


To avoid the building up of sugar and dirt in the

harvesting equipment and to preserve the grape

harvesting quality, the machine must be washed

once or several times a day, and above all at the

end of the work.

The self--propelled machine washing must take

place with standstill thermal engine; anyway, for

cleaning the harvesting equipment in the best way,

it is necessary to start the norias, the conveyors

and the extractors, after having positioned the ma-

chine in a stable place. This is anyway a depar-

ture from the general safety requirements

specified in the Operator’s Manual.

This operation calls for close attention and strict

adherence to the following rules:

SECTION 00 - MAINTENANCE - CHAPTER 1 9

� first of all, this operation must be made by a

single operator, skilled in the control of this

machine.

� The machine should be placed in a stable

cleaning area, preferably on a level con-

crete floor measuring at least 5x8 m, pro-

vided with drainage facilities and consistent

with current environmental protection re-

gulations.

The cleaning area should be equipped with the

following:

� a hose with min. diameter 35 mm, long

enough to enable the washing all around the

machine;

� a sufficient flow of water to provide a 2--m jet,

or alternatively a heavy--duty pumping unit

with3to4m 3 capacity water storage tank;

� an adjustable nozzle to direct the water jet to

about 5 m;

� a ladder, 3.5--m high and a 0.7--m long hook.

NOTE: the use of a high pressure cleaning machine

is definitely not recommended.

WASHING THE MACHINE

PREPARING THE MACHINE FOR THE

WASHING AT THE END OF THE CAM-

PAIGN

Before emptying the last hoppers, stop the thermal

engine.

-- Getoffthedriver’sseatand,frominsidethe

harvesting machine, scroll the harvested prod-

uct gathered around the shaking plates and the

rear frame into the buckets.

-- Make an inspection all the machine round and,

starting from the ground, remove any impu-

rities or deposits sticking to the surfaces.

-- Climb onto the driver’s seat, start the thermal

engine, the extractors, the conveyors and the

norias in washing position. Run the engine for

10 seconds, then empty the hoppers.

604 82 321 00 -02 - 2005


10 SECTION 00 - MAINTENANCE - CHAPTER 1

After entering the washing area, lower the machine

to 10 cm from the ground and tilt the hoppers fully.

Make sure the inching lever is in neutral, engage

the hand brake, stop the thermal engine, get off

the tractor and position the hopper safety stops.

-- Place the ladder at the rear of the machine and

climb onto the rear arch. Using the hook, pull

off any vine shoots built up or sticking to and

around the plastic safety cover.

-- Shift the ladder and lay it against the pipe

where the side plates are fastened, so as to

release the elastics holding the plates and

make the residues behind fall down.

Make sure that the plate upper part folds

correctly against the lower one, to prevent

it from being trapped in the hoppers during

tilting.

This operation must be carried out on both ma-

chine sides.

-- Remove the ladder and the hopper stops.

-- Detach the elastics from the rear sealing plates

and remove any debris trapped behind.

-- Remove any plastic plugs sealing the lower

rear part of the norias.

-- Climb onto the driver’s seat and operate the

engine at medium speed, lower the hoppers,

engage the extractors and conveyors, then

place the norias in the washing position.

-- Get off the tractor, leaving the harvesting ma-

chine working parts in operation.

604 82 321 00 -02- 2005

WASHING (in the washing area)

this is a departure from

CAUTION:

general safety requirements specified in the

the

Operator’s Manual.

-- Open the water supply valve, pick up the hose

without the nozzle and climb onto the harvest-

ing machine operating platform located behind

the driver’s seat. From here, thoroughly wash

the top of the machine, the conveyors, the

hopper augers, the norias, etc. for about 10

minutes.

-- Get off the machine and, starting from the

ground, clean the inside of the tunnel from the

front of the harvesting machine:

� plates, shaking frame, shakers;

� then, inject water into the front LH and RH

baffles through the holes provided.

-- Now go to the back of the machine, open the

saloon doors and clean the rear part of the

harvesting machine tunnel:

� the shaking frame assembly, paying special

attention to the shaker connecting rods;

� the plates and the lower sealing sheets.

-- Inject water through the side openings in the

conveyor housings.

-- Sprayalotofwaterinthehoodsofthelower

extractors, remaining at a sufficient distance

from the stalk choppers.

the extractor rotors are

DANGER:

with stalk chopper knives.

fitted

Do not try and fit the pipe or the nozzle when the

thermal engine is running.


-- Now wash the rear outer part of the machine,

SECTION 00 - MAINTENANCE - CHAPTER 1 11

carefully cleaning the inside of the rear deflec-

tors. Inject water into the rear LH and RH de-

flectors through the holes provided.

-- Lay down the hose (shutting off the water sup-

ply, if necessary) and climb onto the tractor.

Raise the RH hopper for about 50 cm, just

enough to uncover the extractor intake hood.

-- Place the left hopper in the same position.

-- Increase the engine speed to maximum.

-- Get off the tractor, retrieve the hose and climb

onto the harvesting machine platform. Wash

the inside of the extractors by flooding them

with water, one after another, at 7--second in-

tervals.

-- Get off the harvesting machine platform, shut

off the water supply, climb onto the tractor and

stop the harvesting functions (extractors, con-

veyors and norias).

Option

At this stage you can check the extractor

chutes for cleanliness by opening the in-

spection doors provided. First make

sure that the stalk choppers have come

to a complete stop.

-- Operate the machine to empty the hoppers

and return to the washing area.

-- Raise the machine to mid--height and tilt the

hoppers completely, stop the thermal engine

and engage the parking brake.

-- Getoffthetractor,fitthenozzletothewater

hose and open the water supply. One side

after the other, direct the jet toward and around

each conveyor, paying special attention to the

lateral opening of the conveyor housings, to

the plates, etc...

-- From the back side of the machine, wash the

hoppers and the hopper auger ends.

� Inspect the machine again and wash the

wheel links, the wheels, the safety covers,

the lower extractor outlets, the cab, etc..

� Shut off the water supply and open the con-

veyor housing inspection doors through the

inside of the harvesting machine tunnel.

-- Climb onto the tractor, start the engine and set

it to idling. Lower the machine keeping the

hoppers lifted, start the extractors, the con-

veyors, the shaking and norias in washing

position. Operate the machine for 2 to 3 min-

utes to allow the water to drain off.

After cleaning has been completed, the machine

will be ready for daily lubrication.

NOTE: after greasing, remember to reposition the

inspection doors, the plates, etc... which were

opened during the washing operations.

604 82 321 00 -02 - 2005


12 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 13

HYDROSTATIC AND HYDRAULIC SYSTEM MAINTENANCE

1) Intake and return filter cartridge replace-

ment

This cartridge must be replaced:

a) every 800 hours,

b) or every two years,

c) at each discharging.

2) Draining and refilling the circuit

Drain the circuit every 800 hours and at least every

two campaigns.

Always observe the following recommendations:

a) fill the oil reservoir completely with the recom-

mended oil immediately at the end of the cam-

paign, to prevent condensate from forming be-

tween two seasons.

The oil must be filled by means of a pump

through the quick return coupling, so as to filter

the oil, or through the suitable fitting.

b) Before the following campaign and, compulsor-

ily, before starting the thermal engine, empty

the tank partially to ensure a perfect oil settling.

c) Check the oil level in the reservoir.

IMPORTANT: when topping oil up, use the same

type used for the initial filling.

When draining oil, work with great care and cleanli-

ness. Clean by a jet of compressed air or a clean

brush and oil the drain and filling holes before disas-

sembling them, so that no foreign impurities or

matters enter the circuit.

Remove the drain nut under the reservoir. Empty the

reservoir only.

During drain operations, replace the cartridges of the

intake filter and of the return filter.

604 82 321 00 -02 - 2005


14 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


ROUTINE MAINTENANCE

Engine

SECTION 00 - MAINTENANCE - CHAPTER 1 15

-- Oil change every 400 hours or once a year

(incaseofACEAE3orE5oil).

-- Oil and fuel filter change every 400 hours

or once a year.

-- Belt tension adjustment every 400 hours or

onceayear.

-- Level check and cleaning of the radiator

core every day, or every 10 hours.

-- Tappet adjustment every 1200 hours (see

section 10).

-- Injector calibration adjustment every 1200

hours (see section 10).

IMMEDIATELY AFTER EACH CAMPAIGN

Disassemble:

-- the shakers without the link rods

-- the right and left bucket chains

-- the conveyor belts.

Carefully clean the above assemblies.

Repair broken buckets and removed small blocks.

in a ventilated room, protected against ro-

Store

dents:

the bucket chains, which should be ex-

--

to prevent bucket deformation.

tended

the conveyor belts, which should be laid

--

transversely.

out

-- the shakers, which should be laid out flat.

Carefully clean the rail assembly and the conveyor

bodies, using a water jet. Drain the inside water.

Check that no harvest residue remains in the ma-

chine.

WINTER STORAGE

Hydraulic system

-- Oil change every 800 hours or every 2

years.

-- Oil filter change every 800 hours or every

two years.

-- Protection sleeve condition control.

-- Detection and repair of possible leaks.

-- Priming and exchange pressure control.

Mechanical system

Wheel tightening check (see section 44)

every 50 hours and then every 400 hours.

Steering limiter adjustment check (see sec-

tion 41) every 50 hours and then every 1200

hours.

AFTER WASHING

for wear on the inner side of the rails and

Check

slides.

the machine assembly (self--propelled ma-

Grease

+ harvesting machine).

chine

the harvesting devices (shaking, con-

Operate

etc...) for half an hour.

veyor,

all the grease fittings on the harvesting ma-

Refill

(shaker link rods, shaking system controls,

chine

front plate and bottom roller greasers).

Replace the worn or damaged parts.

the machine (or just the harvesting machine)

Store

a covered, closed and dry area.

in

the machine on blocks to relieve the tyres,

Support

whichshouldbeleftinflated.

up the paintwork as necessary and replace

Touch

defaced safety decals.

any

the operation of the steering valve (push

Check

return).

button

Retract all cylinders and grease all unpainted

mechanical parts (shafts, pins, adjustment rods,

cylinder rod outlet ends, rails, slides, antiskid valve

push button, etc...).

604 82 321 00 -02 - 2005


16 SECTION 00 - MAINTENANCE - CHAPTER 1

Self -propelled machine not used as multi -

function

Completely fill the fuel tank and the hydraulic res-

ervoir to prevent condensation.

Make sure the concentration of antifreeze in the

cooler is sufficient for local temperature conditions.

Change the thermal engine oil and the oil filters.

Bleed the fuel filters.

Seal the intake and exhaust ports, making them

tight.

Detach the battery, clean and recharge it. Grease

the terminals with acid--proof grease.

604 82 321 00 -02- 2005

ONCE A MONTH:

-- remove a small amount of oil from the hydraulic

reservoir.

-- Remove the intake and exhaust port guards.

-- Assemble the battery again.

-- Operate the engine on road and let it run for the

time required to reach a temperature by about °.

-- Operate all the machine parts (extractors, con-

veyors, lifting, steering, ...).

-- Operate the cab air conditioning system.

-- Stop the engine.

-- Top up the hydraulic reservoir.

-- Remove the battery.

-- Refit the intake and exhaust port guards.


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 1

SECTION 05 - MACHINE PREPARATION AND EQUIPMENT

Chapter 1

CONTENT

Description Page

......................................................

Section

adjustment 2

...........................................................

Console

604 82 321 00 -02 - 2005


2 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005

22 mm

B

7�

A

45 mm


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 3

INCHING CONSOLE

1) This console can be adjusted forwards and backwards by 45 mm. To this purpose, loosen the two lock--

nuts (A) and the screw located inside the housing.

2) The inching lever can be adjusted as for its height -- 22 mm -- and its sloping is adjustable by 7�; tothis

purpose, loosen the three screws (B).

CHECKS

Check all levels:

-- engine oil

-- hydraulic oil

-- coolant

-- windscreen washer fluid

Check all the machine functions.

SHAKER ASSEMBLY

After analyzing the vineyard structure, assemble the shakers following the instructions of section 58.

604 82 321 00 -02 - 2005


4 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 10 - ENGINE - CHAPTER 1 1

SECTION 10 - ENGINE

Chapter 1 - Engine

CONTENT

Operation Description Page

specifications 2

.........................................................

General

5

.........................................................................

Data

torques 15

...........................................................

Tightening

17

.......................................................................

Tools

views 18

................................................................

Engine

diagram 20

..........................................................

Lubrication

diagram 22

.............................................................

Cooling

diagnosis 26

..............................................................

Fault

001 30 Engine. Compression Test 30

.....................................................

10

001 53 Engine D.A. Checks, measurements and repairs 31

.................................

10

102 70 Crankshaft front seal -- Replacement 94

...........................................

10

102 74 Crankshaft rear seal -- Replacement 96

............................................

10

106 12 Valve tappet and rocker arm clearance -- Adjustment 100

.............................

10

218 30 Engine injector R.I. 101

..........................................................

10

246 14 Bosch injection pump R.I. Timing. Air bleed 102

.....................................

10

402 10 Coolant pump R.I. 110

...........................................................

10

402 30 Thermostat valve R.I. 112

........................................................

10

414 10 Coolant pump and generator drive belt. Tension adjustment 113

.......................

10

604.82.321.00 -02 - 2005


2 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Engine, technical type:

model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601

--

pump)

(BOSCH

604.82.321.00 -02- 2005

Seedataonpage6

-- model VL610 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL620 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL630 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL640 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL660 -- type F4GE0684C*D600 (BOSCH pump) Seedataonpage9

Cycle ............................................... diesel, 4--stroke

Fuelinjection ........................................

Direct

Numberofcylindersinline............................. 4 6

Piston diameter

mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620 -- VL630

--

................................. 4.094 in. (104 mm)

--VL640--VL660

Pistonstroke ........................................ 5.197 in. (132 mm)

Total displacement:

-- modelVM460--VM370--VL570 .................... 4485 cm 3

-- mod.VL610--VL620--VL630--VL640--VL660 ...... 6728 cm 3

ratio for Mod. VM460 -- VM370 -- VL570 --

Compression

VL620--VL630--VL640--VL660 .............. 17,5:1

VL610--

Maximum power:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 94 kW (128 HP)

-- modelVL610--typeF4GE0684G*D600 .............. 107 kW (145 HP)

-- modelVL620--typeF4GE0684G*D600 .............. 107 kW (145 HP)

-- modelVL630--typeF4GE0684E*D600 .............. 120 kW (160 HP)

-- modelVL640--typeF4GE0684E*D600 .............. 120 kW (160 HP)

-- modelVL660--typeF4GE0684C*D600 .............. 129 kW (175 HP)

Maximumpowerspeed ............................... 2300 rpm

Maximum torque: model VM460 -- VM370 -- VL570 -- type

--

F4GE0484C*D601

500 (Nm)

-- Maximum torque: model VL610 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL620 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL630 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL640 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL660 -- type F4GE0684C*D600 700 (Nm)

Maximumtorquespeed ............................... 1400 rev/min

Numberofmainbearings .............................. 5 7

Sump ............................................... steel

(continued)


SECTION 10 - ENGINE - CHAPTER 1 3

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Lubrication ........................................... forced, with gear pump

Pumpdrive ............................................ camshaft

Enginespeed/oilpumpspeedratio ....................... 2:1

with mesh filter on oil intake and cartridge

Oilfiltering.............................................

on delivery line

filter

Normal oil pressure with motor warmed--up

atslowidling........................................... 10.15 psi (0.70 bar)

atfastidling ........................................... 50.76 psi (3.50 bar)

Cooling .............................................. coolant circulation

on mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620

Radiator

VL630--VL640--VL660 ............................... Engine coolant and hydraulic circuit fluid

--

Fan,drivenbyahydraulicmotor.......................... suction, steel with 8 blades

Coolantpump..........................................

Coolantthermometer ...................................

Temperature ranges corresponding to each section:

-- greensector(normalconditionsofuse) ..................

-- redsector ...........................................

At 221 °F (105°C) every minute

Caution!

230 °F (110°C) every 10 seconds

under

centrifugal vane--type

with 12 segments

104 °F --212°F (40°C --100°C)

212 °F --248°F (100°C --120°C)

Enginespeed/coolantpumpspeedratio ................... 1:1,977

Temperaturecontrol .................................... via thermostat valve

-- initialopening....................................... 177.8 ± 35.6 °F (81± 2 °C)

system ........................................ overhead valves operated by tappets, rods

Timing

rocker arms via the camshaft located

and

Intake:

(cont)

the engine block; the camshaft is driven

in

the crankshaft using straight--tooth

by

gears

-- start:beforeT.D.C. .................................. 15°

-- end:afterB.D.C. .................................... 35°

Exhaust:

-- start:beforeB.D.C. ................................. 69°

-- end:afterT.D.C. .................................... 21°

Clearance between valves and rocker arms with engine cold:

-- intake ............................................. 0.009 ± 0.001 in. (0.25 ± 0.05 mm)

-- exhaust ............................................ 0.019 ± 0.001 in. (0.50 ± 0.05 mm)

For further timing system technical data ................... see page 12

(continued)

604.82.321.00 -02 - 2005


4 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Fuel system

with dual cartridge dry air filter, with

Airfiltering.............................................

filter indicator

clogged

Fuelpump............................................. with double diaphragm

........................................... through wire filter in fuel supply pump, and

Fuelfiltering

cartridge on delivery line to

replaceable

604.82.321.00 -02- 2005

injection pump

Camoperated ......................................... engine timing

BOSCHinjectionpump.................................. rotating distributor type

All--speed governor, incorporated in pump:

BOSCH ............................................... centrifugal counterweights

Automatic advance regulator, incorporated in pump:

BOSCH ............................................... hydraulic

For further fuel system technical data:

advance (pump setting for start of delivery before TDC)

Fixed

Pressure setting -- Injection order, and other information

--

............................. refer to the data for the relevant engine

regardingtheBOSCHpump

in the table on page 2

type

(cont)


Turbocharger:

SECTION 10 - ENGINE - CHAPTER 1 5

FUEL SYSTEM DATA

For version F4GE0484C*D601:

--

.............................. GKB13L/A085BXL

--typeHOLSETHX27W

For versions F4GE0684C*D600 -- F4GE0684E*D600 --

--

F4GE0684G*D600:

--typeHOLSETHX35W ..............................

E7735AG/E16XB11

......................................... rotating distributor with speed governor

Injectionpump

advance regulator incorporated

and

BOSCH pump:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 VE 4/12 F 1150 L 956 -- 504053467

-- modelVL610--typeF4GE0684G*D600 ................ VE 6/12 F 1150 L 964 -- 504060083

-- modelVL620--typeF4GE0684G*D600 ................ VE 6/12 F 1150 L 964 -- 504060083

-- modelVL630--typeF4GE0684E*D600 ................ VE 6/12 F 1150 L 981 -- 504060084

-- modelVL640--typeF4GE0684E*D600 ................ VE 6/12 F 1150 L 981 -- 504060084

-- modelVL660--typeF4GE0684C*D600 ................ VE 6/12 F 1150 L 978 -- 504053466

Directionofrotation ..................................... anticlockwise

.........................................

Injectionorder

modelVM460--VM370--VL570 ...................... 1--3--4--2

--

-- mod.VL610--VL620--VL630--VL640--VL660 ........ 1--5--3--6--2--4

Fuel injectors:

BOSCHtype.............................

VM460

VM370

VL570

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 . 504063465

F4GE0684E*D600

DSLA

P 1174

145

VL610

VL620

504063465

DSLA

145 P 1174

VL630

VL640

504063465

DSLA

145 P 1174

VL660

504063465

DSLA

145 P 1174

Numberofnozzleholes ................... 6 6 6 6

Nozzleholediameterin.(mm.) .............

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 .

F4GE0684E*D600

0.009

(0.223)

.............. 3771 to

Calibrationpressurepsi(bar)

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

604.82.321.00 -02 - 2005


6 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VM460 - VM370 - VL570 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 4/12 F 1150 L 956

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1150 0.091 -0.138

1.1

-3.5) (2.3

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1.../2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 73.5 -79.5 cc/1000 0

Difference

cc/1000

700 103.5 -109.5 cc/1000 1000 3.5

1.4 Minimum 400 6.5--18.5 cc/1000 0 6.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1280 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(11.0--21.0) - (0 .3 -- 0.5 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1150

0.091--0.138 (2.3--3.5)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1280 max. 3.0 1000

p p p

Lever

-

-

1150 95.0--101.0 1000

700 103.5 -109.5 1000

700 88.0 -94.0 500

500 73.5 -79.5 0

Minimum 400 6.5--18.5 0

450 max. 3.0 0

curve 100 > 80.0 0

g Starting

300 < 93.5 0

-

-

-

--

--

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

-


SECTION 10 - ENGINE - CHAPTER 1 7

VL610 - VL620 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 6/12 F 1150 L 964

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1000 0.063--0.110

1.1

-2.8) (1.6

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1.../2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 86.2 -92.2 cc/1000 0

Difference

cc/1000

700 80.8 -86.8 cc/1000 1000 3.5

1.4 Minimum 360 7.0--23.0 cc/1000 0 5.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1290 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(6.0--16.0) - (0 .4 -- 0.6 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1000

0.063--0.11 (1.6--2.8)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1290 max. 3.0 1000

p p p

Lever

-

-

1150 75.0 -81.0 1000

900 80.8 -86.8 1000

500 92.5 -98.5 325

500 86.2 -92.2 0

Minimum 360 7.0--23.0 0

420 max. 3.0 0

curve 100 > 80.0 0

g Starting

250 < 107.0 0

-

-

-

1150

2.1--3.3

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

604.82.321.00 -02 - 2005

-


8 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VL630 - VL640 - CALIBRATION DATA

MODD.

BOSCH INJECTION PUMP TYPE VE 6/12 F 1150 L 981

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

Источник: [https://torrent-igruha.org/3551-portal.html]

MONDAY, OCTOBER 20, 2014   9:00-17:00

POSTER PLUS VIDEO I – Poster Exhibition – Hall XL__________

P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN; COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY

N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1, S. Date1, J. Bapaye3

1Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale Medical College, Pune, India

Contact E-mail Address:[email protected]

INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis. The best approach for drainage of these collections is still controversial. We present our retrospective data comparing the two endoscopic methods for drainage of WOPN.

AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural drainage (EUTMD) using a newly designed fully covered large-bore wide-flare metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who underwent placement of multiple plastic stents (Gr II). The pre-op CECT confirmed suitability of endoscopic drainage based on location, wall thickness & contents. Visual quantification of necrosis (>50% solid debris) by EUS excluded 8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by standard technique by a single endoscopist. The difference between the two groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of NCT and subsequent necrosectomy was done whenever necessary. Follow-up imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes were compared in terms of clinical success, need for surgery, complications, hospital stay and mortality.

RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of demographics, etiology of pancreatitis, cyst location, size and amount of debris. Placement of NCT, need of necrosectomy and no of sessions required were also not different between the two groups. Clinical success defined as resolution of symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p = 0.048). None of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II (p = 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p = 0.016)

Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p = 0.012). Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p = 0.22)

CONCLUSION: The Nagi stent™ is effective and safe for EUTMD of WOPN. It permits rapid clinical resolution with 100% technical and clinical success rates. It offers distinct advantage over plastic stents although further prospective studies are warranted.

Disclosure of Interest: None declared

P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF THE ESOPHAGUS USING A “RENDEZ-VOUS” TECHNIQUE

J.-M. Gonzalez1,*, G. Vanbiervliet2, M. Barthet1

1Gastroenterology, Aix-Marseille University, North Hospital, Marseille, 2Gastroenterology, Nice Hospital, Nice, France

INTRODUCTION: Complete esophageal obstruction leads to definitive fasting. The rendez-vous endoscopic approach had already been described for complex stenoses as an alternative to surgery that has high morbid-mortality.

AIMS & METHODS: This is a case series report about six patients referred for complete esophageal disruption classified in two groups: 1/ Long disruption (> 5cm), one after caustic ingestion and two due to an esophageal stripping during SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (< 5cm), consecutive to radiation therapy for a neck neoplasia. They had been fasting for 3 to 18 months. All the procedures were performed according the anterograde retrograde approach, under anesthesia and with CO2 insufflation and X-rays guidance.

RESULTS: There were 3 men and women between 25 and 71 years old. All the reconstructions have been successful in one to three endoscopic sessions, using the non hydrophilic tip of a guide wire passed through a straight catheter in 5 cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created, by transillumination (n = 1) or head and neck surgery (n = 1). In order to guide the reconstruction, SEMS was used in one case, NGT in one case, and both were used in one patient. The first dilation was performed with a CRE balloon (12-15mm). All the patients could eat mixed after 2 POD. There was no intra-operative or post-operative complication. Then, the patients underwent 3 to 18 dilations sessions during 1.5 to 15 months; two are still undergoing dilations and all eat normally.

CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe and effective in case of esophageal disruption even with loss of SES, avoiding surgery.

Disclosure of Interest: None declared

P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY GASTRIC CANCERS USING THE CLUTCH CUTTER

K. Akahoshi1,*, Y. Motomura1, M. Kubokawa1, J. Gibo1, N. Kinoshita1, S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1, N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1

1Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: To reduce the risk of complications related to ESD using conventional knives, we developed the Clutch Cutter (CC), which can grasp and incise the targeted tissue using electrosurgical current.

AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients (228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intramucosal or superficial submucosal gastric cancer without lymph node involvement, that had been confirmed by preliminary endoscopy, EUS, and endoscopic biopsies, were enrolled into this prospective study. The CC was used for all steps of ESD (marking, circumferential marginal incision, submucosal dissection, and hemostatic treatment). The therapeutic efficacy and safety were assessed.

RESULTS: The mean size of the early gastric cancers and resected specimens was 17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes. The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respectively. The R0 resection rates according to tumor size and location were 97.4% (229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9% (127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/95) in upper portion. The mean operating time according to tumor size and location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9 min in lower portion, 108.8 min in middle portion, and 117.2 min in upper portion. Perforation during ESD occurred in one case (0.3%), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully treated by endoscopic hemostatic treatment.

CONCLUSION: ESD using CC is a safe and technically efficient method for resecting early gastric cancers.

REFERENCES

1) Akahoshi K, Akahane H, Murata A, et al. Endoscopic submucosal dissection using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.

2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic submucosal dissection using the clutch cutter for early stage digestive tract tumors. Digestion 2012: 85: 80-84.

Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM have applied for the patent in Japan, Europe, and USA for the Clutch Cutter described in this article. China has already granted the patent., Y. Motomura: None declared, M. Kubokawa: None declared, J. Gibo: None declared, N. Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T. Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya: None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M. Oya: None declared

P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS

M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T. Ponchon5

1Gastroenterology and endoscopy, Hôpital Edouard Herriot, 2Inserm U1032, 3Functional disorders unit, Hôpital Edouard Herriot, Lyon, France, 4Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania, 5Gastroenterology and endoscopy unit, Hôpital Edouard Herriot, Lyon, France

Contact E-mail Address:[email protected]

INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising method for the treatment of the esophageal achalasia. But the precise technique can be refined. We developed a combined technique of water jet system for tunnelling and hook knife section for myotomy and we evaluated its results in a prospective study.

AIMS & METHODS: The patients presented with an achalasia without any prior instrumental treatment. The submucosal tunnel was created 12 cm over the cardia and 3 cm below, and then the endoscopic myotomy was performed using the Olympus Hook Knife by a single operator with CO2 insufflation, beginning 8 cms over the cardia and finishing 2 cms below. The clinical evaluation was realized before and then after the procedure at 1, 3, 6 and 12 months (score of Eckardt, score of quality of life GIQLI). A high-resolution manometry was realized before POEM and 3 months later to classify the achalasia (classification of Chicago) and to measure basal pressure and pressure of relaxation integrated (PRI) of the lower esophageal sphincter. Then an esophageal pHmetry of 24 hours was performed at 3 months to diagnose GERD. The data are expressed in median (extremes) and compared before and later myotomie by paired t-test.

RESULTS: 21 patients (13 men, average age 61 years) were included. 18 procedures were complete, 1 was not realized because of a large esophageal diverticulum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries occurred but did not prevent to continue the procedure after mucosal closure by clips. Dual Knife ® (n = 7) or the water jet Nestis Enki 2 ® (n = 11) were used for the tunnel. No mucosal injuries were observed with the water-jet system. Hook Knife ® was used for all myotomies. The average time of procedure was 94.2 min with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated with a needle during the procedure in 13 cases without any visible perforation. CT scan at day 1 showed a pneumomediastinum (n = 14/18), a pneumoperitoneum (n = 14/18) and/or a peumothorax (n = 3/18). No sepsis was observed. Feeding was always possible with liquids at day 1. All patients noted a clinical improvement. At 3 months, the basal pressure of the SIO was decreased for all patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p<0.01) as well as the PRI (8 mmHg (0-16) against 23 mmHg (9-28), p<0.01). pH metry showed a pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases.

Inclusion1 month3 months6 months1 year
n211714103
Eckardt6 (3-11)1 (0-3)*1 (0-3)*0 (1-4)*0 (0-0)*
GIQLI82 (50-114)115 (66-135)*115 (82-140)*131 (94-143)*140 (130-142)¥

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CONCLUSION: Water-jet injection allows rapid and safe tunneling of the submucosa and myotomy with hook knife is very precise. Safety and effectiveness of mytomy is reinforced using these technical refinements.

Disclosure of Interest: None declared

P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGH-MAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY FOR DIFFERENTIATION OF GASTRIC LESIONS

R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3, E. Nikonov4, V. Kapranov5, A. Rusakov6

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation, 2Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G. Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic №1 of the Business Administration for the President of Russian Federation, Moscow, 5Internet Center, 6Administration, P. G. Demidov Yaroslavl State University, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: High-magnification endoscopy with narrow-band imaging (HME-NBI) has been used for diagnosis of gastric pathology because of its high accuracy. Nevertheless, the application of these advanced techniques in clinical practice is difficult due to the presence of various histological changes of gastric mucosa with different modifications of microvascular and microsurface patterns. Newly developed computer-aided decision support systems are designed to detect and/or classify abnormalities and thus assist a medical expert in improving the accuracy of medical diagnosis. However, there is lack of data for computer-aided devices for classification of gastric lesions with HME-NBI.

AIMS & METHODS: The aim of this study was to evaluate the effectiveness of computer-aided classifier of endoscopic magnification images of gastric lesions. We analyzed our database contains 78 endoscopy NBI magnification images of gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images were classified into three classes: oval (13 images), tubular (31 images), and destroyed with vessel network (34 images). Initially we divided images of every class into two sets — training set and test set. Then we selected uniformly distributed random points with fixed density (one random point for every 300 pixels) at every picture, which were analyzed by extracting topological features for building the classifier. Training set images were used for classifier training with Adaboost algorithm and testing set images of each group were utilized for testing with previously trained classifier. We repeated the procedure described above for the estimation of classifier quality.

RESULTS: From 78 database images there were 50 images (66.6%) with the success rate of correct classification exceeding 80%. In 14 images (17.9%) all points (100%) were recognized correctly. The mean percentage of points with the correct classification was 79%.

CONCLUSION: Topological features were successfully used for description of endoscopic magnification images. The combination of topological features analyzed with Adaboost algorithm allowed for creating and effective training of computer-aided classifier of endoscopic magnification images of gastric lesions.

Disclosure of Interest: None declared

P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS CONDITIONS AND LESIONS OF THE STOMACH

R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration, Polyclinic №1 of the Business Administration for the President of the Russian Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: Endoscopic mapping of the entire stomach with advanced techniques has been recommended as an important step of surveillance of premalignant gastric conditions/lesions [1]. Although current imaging technologies, such as narrow-band imaging (NBI) and high-magnification endoscopy, allow enhanced visualization of gastric mucosa, their application is still limited due to low contrast and brightness of endoscopic view and complexity of usage. Newly developed NBI system with dual focus (DF) magnification might be a promising tool to overcome this challenge.

AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy of new NBI-DF system in detection, characterization of gastric lesions in patients with extensive atrophy and/or intestinal metaplasia. A total of 43 patients (mean age 51.3 years, SD = 12.1) were initially examined by conventional white light endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy (CE) with indigocarmine was performed as the “gold standard” for detection of lesions. Any suspicious areas detected by NBI or CE were subsequently further assessed with NBI with DF (Olympus Exera III GIF H190) and characterized accordingly. Biopsies were taken from all lesions for histological assessment.

RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic (chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 high-grade dysplasia/early gastric cancer. All lesions (100%) detected by CE were found with NBI observation. Endoscopic histology prediction was successful in 88 cases (94.6%) Endoscopic misdiagnosis was found in 5 cases (5.4%): overestimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive predictive value and negative predictive value were 80%, 97.4%, 85.7% and 96.2% respectively for early gastric cancer/high-grade dysplasia.

CONCLUSION: Observation of gastric mucosa with a novel NBI system was at least as effective as CE with indigocarmine in detection of suspicious gastric lesions in patients with precancerous conditions and lesions of the stomach. Dual focus magnification provides sufficient assessment of microvascular and microsurface patterns in order to differentiate gastric lesions. Further randomized controlled studies are needed to be performed for clarifying the role of novel endoscopic system in diagnosis of gastric pathology.

REFERENCES

1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.

Disclosure of Interest: None declared

P0007 DEVELOPMENT OF A PROTOTYPE OF VIDEO SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES DURING ENDOSCOPIC EVALUATION OF BARRETT’S OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL STUDY

S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1

1CHU Strasbourg, 2IRCAD, Strasbourg, France

Contact E-mail Address:[email protected]

INTRODUCTION: The prevalence of Barrett's oesophagus (BE) is 5 to 6% in the general population, with a progression from dysplasia to adenocarcinoma 0.6 to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early lesions accessible to endoscopic treatment. However, the relocalisation of lesions detected by biopsies may be difficult during follow-up endoscopies. The purpose of this study was to evaluate the prototype of a magnetic probe for accurate location of the position of the endoscope, allowing the relocalisation of this position in a subsequent endoscopy. We report the results of a feasibility study in pigs and the use of this device in two patients with BE.

AIMS & METHODS: The system consists of an electromagnetic (EM) field transmitter and an EM probe constituting the electromagnetic tracking system (EMS) (NDI, Aurora). The EM probe is inserted through the operating channel of a double channel gastroscope. The EM field generator is positioned on the patient's chest wall. The system also includes new software developed at IHU/IRCAD, which performs simultaneous recording of the video from the endoscope alongwith its corresponding position, as measured by the EMS. During a second endoscopy, this software allows automatic synchronisation of the recorded video to provide relocalisation of the endoscope in front of previous biopsy sites in the oesophagus.

The system was tested in 5 anesthetised pigs. During the first endoscopy, ten markings were performed by argon plasma electrocoagulation (ERBE Tübingen, Germany) in the distal oesophagus. The position of each marking was recorded by the system. A second operator to then performed a blind endoscopy on the same pigs and was asked to follow the system implicitly as a guide to relocate the markings.

In 2 patients with BE, the system was then tested to facilitate relocalisation of the biopsy sites.

RESULTS: Ten markings were made in the distal oeosphagus of 5. After withdrawal of the endoscope the second operator found 48 of the 50 markings (96%) using the guidance provided by the system. The positioning of the endoscope provided by the EMS system was within a 2mm range from the initial positionning. In the evaluation of BE patients, the system relocalised the biospy sites within a range of 3mm.

CONCLUSION: This preliminary study shows the feasibility of the EMS prototype to relocalise the endoscope in the oesophagus within an acceptable range. The clinical usefulness of this system should be evaluated further during the follow-up of patients with BE.

Disclosure of Interest: None declared

P0008 THE UTILITY OF ROUTINE CHROMOENDOSCOPY FOR DETECTION OF DYSPLASTIC LESIONS DURING SURVEILLANCE COLONOSCOPY IN PATIENTS WITH COLONIC INFLAMMATORY BOWEL DISEASE. DOES RESEARCH TRANSLATE TO CLINICAL PRACTICE?

U. Javaid1, R. Thethi1, P. Luthra1, N. Mohammed2,*, J. Hamlin1, B. Rembacken1, V. Subramanian2

1Gastroenterology, St James University Hospital, Leeds Teaching Hospital NHS Trust, 2Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective studies to improve dysplasia detection rates by improving the ability to detect subtle mucosal changes. (1) The utility of CE in dysplasia detection in patients with IBD during routine clinical practice has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by CE with standard white light endoscopy (WLE).

AIMS & METHODS: Retrospective cohort study of patients with long standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching Hospital NHS Trust between January 2012 to December 2013. Details of diagnosis, duration of disease and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records and patient notes.

RESULTS: There were 120 colonoscopies in the CE group and 220 colonoscopies in the WLE group. The groups were well matched for all demographic variables. 27 dysplastic lesions were detected in 20 patients in the CE group and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the lesions were detected on targeted biopsy and harboured low grade dysplasia. The adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic lesion was 4.6 (95% CI 1.6-13.7) in favour of CE.

CONCLUSION: CE colonoscopy improves detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD even in routine clinical practice, confirming data from prospective trials. CE should be the standard of care for all IBD surveillance procedures as advocated by both BSG and ECCO guidelines.

REFERENCES

(1) Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 304-312.

Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014   9:00-17:00

LIVER & BILIARY I – Poster Exhibition – Hall XL__________

P0009 INVOLVEMENT OF B-CELLS IN HEPATIC INFLAMMATION DURING NONALCOHOLIC STEATO-HEPATITIS (NASH)

A. Jindal1,*, S. Sutti1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1 on behalf of Laboratory of General Pathology, Prof. Albano, Novara, Italy

1Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Growing evidence indicates that adaptive immunity contributes to the process leading to chronic hepatic inflammation in NASH. However, the mechanisms involved are still incompletely characterized. Recently, B-lymphocytes have emerged as players in orchestrating adipose tissue inflammation in obesity contributing to the development of insulin resistance.

AIMS & METHODS: We investigated the possible role of B-cell responses in the pathogenesis of NASH. NASH was induced by feeding four weeks C57BL/6 mice with a methionine-choline deficient (MCD) diet.

RESULTS: In mice receiving the MCD diet the development of steatohepatitis was associated with an increased hepatic infiltration by B220 (CD20) positive B-lymphocytes and by the detection of circulating IgG targeting oxidative stress-derived antigens such as malonildialdehyde- (MDA) and 4-hydroxynonenal-protein adducts. Moreover, immunohistochemistry showed the presence of IgG deposits within the hepatic inflammatory infiltrates that co-localized with MDA-derived antigens, indicating the formation of immunocomplexes. To substantiate the role of oxidative stress in triggering B-cell responses in NASH, mice were immunized with MDA-adducted bovine serum albumin (MDA-BSA) before feeding the MCD diet. In MCD-fed, but not in control mice, MDA-BSA immunization promoted liver B-cell expansion and enhanced transaminase release, lobular inflammation and the hepatic production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-12. Among immunized MCD-fed mice there were also positive correlations between the individual expression of the B-cell marker B220 and those of macrophage M1 activation markers IL-12p40 and iNOS (r = 0.87 and 0.71 respectively; p<0.02).

This effect was likely mediated by B-cell interaction with CD4 T-cells as in the same animals B220 expression also positively correlated with that of IFN-γ (r = 0.76; p<0.03) and of the co-stimulatory molecule CD40 (r = 0.72; p<0.05). Furthermore, depleting CD4+ T-cells in MCD-fed immunized mice by using an anti-CD4 monoclonal IgG did not affected B220 expression, but significantly lowered the hepatic mRNAs IFN-γ, iNOS and IL-12p40 and ameliorated lobular inflammation and focal necrosis.

CONCLUSION: These results indicate that B-cell responses triggered by oxidative stress can contribute to inflammation in NASH by stimulating T-cellular responses.

Disclosure of Interest: None declared

P0010 GENERATION OF A VECTOR CONTAINING AN SHRNA FOR THE RECEPTOR CB1 AS AN ANTIFIBROGENIC STRATEGY IN LIVER DISEASE

A. Díaz Rivera1,*, V. Chagoya de Sánchez 2, G. Velasco Loyden 2, L. García Benavides 3, J. Armendáriz Borunda 1, A. Sandoval Rodríguez1

1Molecular Biology and Gene Therapy Institute, Guadalajara, 2Cellular Physiology Institute, México, D. F, 3Institute of Experimental and Clinical Therapeutics, Guadalajara, Mexico

Contact E-mail Address:[email protected]

INTRODUCTION: Blockade of cannabinoid type I receptor (CB1) by pharmacological antagonist has demonstrated antifibrogenic effects in models of cirrhosis. Gene therapy with a shRNA molecule for CB1 wthinin an adenovirus has the advantage of hepatic tropism, which will reduce side effects and increase the transduction efficiency.

AIMS & METHODS: Design a shRNA that efficiently inhibit the expression of CB1, evaluate its antifibrogenic effect in an experimental model of liver cirrhosis and generate an adenoviral vector coding for the shRNA-CB1.

shRNA sequences were designed to blockade mRNA of CB1 at positions 877, 1232, 1501 (pshCB1-A, B, D). The effectiveness of the shRNA was evaluated by inhibition of the mRNA-CB1 after transfection of the plasmids in primary culture rHSC. To determine the optimum dose for transfection in primary cultures, lipofectamine 2000 and Fugene ® HD were tested using a GFP expressing plasmid (pITR-GFP). Later, we evaluated shRNA mediated-CB1 inhibition in cirrhotic rats intoxicated with CCl4. The plasmids were administrated by hydrodynamic injection in a volume of 4 mL. Then, in animals transfected with the most potent shRNA-CB1, mRNA levels of fibrogenic molecules (TGF-β1, Col 1 and α-SMA) and percentage of fibrotic liver tissue was measured. Finally, Ad5 backbone coding for shRNACB1-1232 or shRNA-Irrelevant was generated by homologous recombination between pshRNA and the pAd / BLOCK-iT ™ DEST.

RESULTS: In vitro shRNA designed to block position 877 and 1232 significantly inhibited mRNA (p> 0.05) CB1 gene expression in 77% and 91%, respectively using Fugene ® HD. The sequence of shRNA-Irrelevant did not affect mRNA expression of CB1. Hydrodynamics-based transfection of shRNA-CB1 via iliac vein in the rat allows efficient and repeatable delivery to the liver. A volume of 4 mL carrying 3 mg/kg was administered in 5-7 seconds. In CCl4 model shCB1-1232 showed major decrease in CB1 mRNA and protein (p<0.05), and in consequence fibrogenic molecules TGF-β1, Col I, α-SMA also reduced (60%, 47% and 77% (p<0.05); respectively). Fibrosis diminished 49% (p<0.05) compared to untreated controls. Thus pshRNACB1-1232 was selected for production of adenovector. Homologous recombination between attL and attR regions between pshRNA-1232-CB1 and pAd / BLOCK-iT ™ DEST allowed the generation of Ad-shRNA1232-CB1 backbone.

CONCLUSION: shCB1-1232 demonstrates CB1 gene and protein silencing in vitro and in vivo, decreasing mRNA levels of key fibrogenic molecules and fibrosis, showing potential to be used as therapeutic strategy for liver fibrosis. Recombinant adenovirus expressing this shRNA will have the advantage of high titers production conserving efficient liver transduction, which will facilitate its therapeutic application in experimental models of liver cirrhosis or even clinical scenarios.

Disclosure of Interest: None declared

P0011 CORRELATION BETWEEN INDIRECT SERUM MARKERS AND MORPHOMETRIC VALUES OF FIBROTIC TISSUE IN PBC

C. Stasi1,*, L. Leoncini1, M.R. Biagini1, S. Madiai1, F. Marra1, G. Laffi1, S. Milani2

1Department of Experimental and Clinical Medicine, 2Department of Biomedical, Experimental and Clinical sciences, University of Florence, Florence, Italy

INTRODUCTION: The accuracy of non-invasive methods for the quantification of liver fibrosis in patients with PBC is still debated. Moreover, the Ludwig’s PBC stages do not represent a measurement of quantitative fibrosis.

AIMS & METHODS: We determined the histomorphometrical measurement of fibrotic tissue and analyzed the accuracy of a number of indirect markers of liver fibrosis for the detection of different histological stages of PBC and the association between indirect serum markers and morphometric values (MV) of fibrotic tissue.

Methods: Sections of liver tissue were stained with hematoxylin/eosin and

Sirius red. Only samples with a > 25 mm length and including at least 11 complete portal tracts were considered adequate for the study. Histomorphometrical measurement of fibrotic tissue was performed on sirius red stained sections of liver biopsies. Area percentage measures of fibrotic tissue were ranked into 4 groups reflecting Ludwig’s staging and compared with values of the following serum markers of liver fibrosis: APRI, LOK, FORNS, FIB-4. The percentage of fibrosis was calculated with ImageJ. All results were expressed as mean ± standard deviation. The numerical comparison of continuous data was performed using the Wilcoxon signed ranks test applied to two-samples. Linear regression analysis between two variables was performed by using Pearson correlation. Statistical significance was set at a value of p<0.05.

RESULTS: We enrolled 50 patients with PBC (mean age, 57±12.30 years; 43 F and 7 M; 8 AMA negative, 42 AMA positive). There were 19 (38%) patients in Ludwig’s PBC stage I, 14 (28%) in stage II, 12 (24%) in stage III and 5 (10%) in stage IV. The morphometric values (Table 1) of fibrotic tissue were significantly different in the various Ludwig’s stages of PBC (p<0.05). Only LOK score was statistically different between stage II and III (p = 0.02). No other significant differences were found in the various Ludwig’s stages of PBC for APRI, FORNS, FIB-4 and LOK scores (Table 1). A statistically significant correlation was found between MV and Forns (R2 = 0.3643, p = 0.0004), MV and FIB-4 (R2 = 0.3945, p = 0.0002), MV and LOK (R2 = 0.3367, p = 0.0010), MV and APRI (R2 = 0.1476, p = 0.0361).

Table 1.

Ludwig's stagesMorphometric valuesFORNSFIB-4LOKAPRI
Stage I0.74% ± 0.653.61 ± 1.620.24 ± 0.260.20 ± 0.160.61 ± 0.76
Stage II3.87% ± 1.54.55 ± 1.80.35 ± 0.390.22 ± 0.180.49 ± 0.35
Stage III6.15% ± 1.685.52 ± 2.060.35 ± 0.160.38 ± 0.190.67 ± 0.44
Stage IV14.06% ± 8.458.05 ± 1.761.00 ± 0.760.69 ± 0.341.24 ± 0.79

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CONCLUSION: Histomorphometric values of fibrotic tissue increase progressively in Ludwig’s stages of PBC, where non-invasive markers do not, and correlate positively with indirect serum markers of liver fibrosis.

Disclosure of Interest: None declared

P0012 THE NGF RECEPTOR P75NTR LEADS TO NEURAL HYPERTROPHY DURING THE DEVELOPMENT OF LIVER CIRRHOSIS AND MALIGNANT LIVER TUMORS

D. Hartmann1,*, S. Werscher1, R. Göß1, S. Teller1, M. Schlitter2, K. Becker2, H. Friess1, G.O. Ceyhan1

1Department of Surgery, 2Institute of Pathology, Technische Universität München, Munich, Germany

Contact E-mail Address:[email protected]

INTRODUCTION: The autonomic nervous system is the involuntary part of the peripheral nervous system and regulates the intestinal motor activity, smooth muscles and exocrine glands. Autonomic nerves that innervate the liver reach the organ via the hepatic hilum and run together with the portal vein, the hepatic artery and the bile duct. In the full clinical picture of liver cirrhosis, no parenchymal innervation can be detected. In addition, malignant liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC), are not innervated.

AIMS & METHODS: The aim of this work is the characterization of a possible hepatic neuroplasticity, including responsible neurotrophic factors. In the present work, a collective consisting of 103 patients (22 patients with normal liver tissue, 23 patients with liver cirrhosis, 45 patients with HCC and 13 patients with CCC) was examined for variations in nerve number and nerve size. In addition, growth factors, such as Growth-Associated Protein (GAP-43) and Nerve Growth Factor (NGF), as well as their receptors TrkA and p75NTR were investigated by immunohistochemistry and qRT-PCR in terms of their involvement in a possible hepatic neuroplasticity.

RESULTS: The multiple comparison of median nerve sizes of the examined entities showed a clearly significant difference. The largest nerves were discovered in HCC samples. However, no difference in neural density was detected. Furthermore, significant differences were observed for the high affinity NGF-receptor TrkA and the low affinity NGF-receptor p75NTR with regards to immunoreactivity and relative expression. The highest p75NTR expression was found in normal liver tissue and both, relative expression as well as immuno-reactivity, decrease with increasing nerve size.

CONCLUSION: The results of the present study suggest that the observed neural changes in the liver are related to active neural remodeling processes. The NGF receptor p75NTR seems to take on a key role in this context. Since p75NTR binds all neurotrophins with low affinity, further research is warranted concerning its involvement in the plasticity of hepatic nerves.

Disclosure of Interest: None declared

P0013 HIGH CONCENTRATION OF FIBROTIC AND INFLAMMATORY MARKERS AMONG PATIENTS WITH SCHISTOSOMAL LIVER DISEASES

E. Sinkala1,2, P. Kelly3,4, E. Sinkala1,2,*

1Internal Medicine, University of Zambia, 2Internal Medicine, TROPGAN, Lusaka, Zambia, 3Internal Medicine, Barts and London, Blizzard Institute, London, United Kingdom, 4Internal Medicine, University Teaching Hospital, Lusaka, Zambia, Lusaka, Zambia

Contact E-mail Address:[email protected]

INTRODUCTION: Worldwide the commonest cause of portal hypertension is cirrhosis, but in tropics it is schistosomiasis. Some parts of Zambia are hyper-endemic with prevalence of 77%. Hepatocellular function is preserved in hepatosplenic schistosomiasis hence prognosis is better than cirrhosis. Liver biopsy can confirm fibrosis but it is invasive.

AIMS & METHODS: This is an ongoing case control study involving 70 cases and 20 controls. All cases had varices and were negative for HIV, hepatitis B and C viruses. Hyaluran was used as a marker of liver fibrosis while TNF receptor 1, sCD14, IL1 beta, IL 6 and CRP were inflammatory markers.

We set out to investigate fibrotic and inflammatory makers in hepatosplenic schistosomiasis patients at the University Teaching Hospital, Lusaka, Zambia.

RESULTS: Eighty patients were evaluated and serology for schistosomiasis was positive in 74 (93%) and negative in 6 (7%). Hyaluran levels compared with controls were higher, p<0.001 (median 111.6ng/ml, IQR 39.1, 240.3). Inflammatory markers were elevated: TNF receptor 1 concentrations compared with controls were higher, p <0.001 (median 3150.1pg/ml (IQR 1703.2, 10460.0), sCD14 values were higher than in controls p<0.001, median 2365.0ng/ml (IQR1744.9, 3128.6). IL 1 beta values were higher than in controls p = 0.013, median 4.3pg/ml (IQR 0.8, 13.2) and so were IL 6 values p = 0.001 (median 15.26pg/ml, IQR 10.15, 38.13). Spearman’s rank correlation of hyaluran and TNF receptor 1 was positive (r = 0.44, p = 0.002) and so was hyaluran and IL6 (r = 0.251, p = 0.045).

CONCLUSION: Schistosomiasis is a leading cause of portal hypertension in Zambia and induces a liver fibrotic marker which could be used to assess disease severity. It seems hepatosplenic schistosomiasis also induces high levels of TNF receptor 1, sCD14, IL1 beta and IL6. These elevated markers could be due to bacterial translocation which needs to be confirmed by markers of bacterial translocation such as LPS.

Disclosure of Interest: None declared

P0014 LIVER FIBROSIS PREVENTION AFTER INTRAMUSCULAR ADMINISTRATION OF MATRIX METALLOPROTEINASE-8 ADENOVIRAL VECTOR IN A MODEL OF HEPATIC FIBROSIS

J. Garcia-Bañuelos1,*, E. Eden Oceguera-Contreras1, D. Gordillo-Bastidas1, A. Sandoval-Rodríguez1, B. Bastidas-Ramírez2, J. Gonzalez-Cuevas1, J. Macias-Barragan1, B. Belinda Gomez-Meda1, J. Armendáriz-Borunda1 on behalf of INNOVARE, Guadalajara, Jalisco, México

1Instituto de Biología Molecular y Terapia Génica, Centro Universitario de Ciencias de la Salud, 2Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico

INTRODUCTION: MMP-8 degrades preferentially collagen type I (collagen of higher proportion of hepatic fibrosis). We delivered MMP-8 gene in to the muscle, using an Adenovirus vector, protein is released systemically and is activated in the liver.

AIMS & METHODS: Our aim was to evaluate profibrogenic gene expression pattern and liver fibrosis prevention.

We used four groups of rats (n = 15): control; thioacetamide (TAA), induced-fibrosis; TAA+AdGFP; TAA+AdMMP8. At the beginning of the fifth week of TAA intoxication, administration of vectors in soleum muscle was accomplished. Sub-groups of rats (n = 5) at the end of first, second and third week after vector administration were sacrificed. Percentage of fibrosis, liver function, gene expression of MMP8, proinflammatory genes (IL1-beta, TNF-alpha), profibrogenic genes (collagen α1(I), CTGF and TGF-beta) and antifibrogenic genes (MMP1 and MMP9), were determined.

RESULTS: After 3 weeks of treatment: In the liver and serum, amount of MMP8 protein was sustained, fibrosis decreased up to 48%, proinflammatory genes expression was modified only at the end of the third week, profibrogenic gene expression decreased (Col α1(I) 4 times, TGF-beta 3 times and CTGF 2 times), antifibrogenic genes expression increased (MMP9 2.8 times and MMP1 10 times). According to Knodell score, a clearly diminution of inflammatory cells infiltration in comparison with counterpart animals treated with AdGFP, could be appreciated.

CONCLUSION: A single dose of AdMMP8 in muscle is enough in order to obtain a stable liver MMP8 protein expression and activity during 21 days. Degradation of collagen in the liver modifies pro and anti-fibrogenic gene expression allowing a restoration of hepatic architecture.

Disclosure of Interest: None declared

P0015 WHOLE-PROTEIN MASS SPECTROMETRY TO IDENTIFY CONGENITAL DISEASE OF GLYCOSYLATION IN END-STAGE LIVER DISEASE

J.C. Jansen1,*, M.van Scherpenzeel2, D.J. Lefeber2, J.P. Drenth1

1Gastroenterology and Hepatology, 2Laboratory of Genetic, Endocrine and Metabolic Disease, Radboud University Medical Center, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Congenital disorders of glycosylation (CDG) are a heterogeneous group of autosomal recessive metabolic diseases with a wide spectrum of clinical symptoms. Depending on localization of the defective protein, two types are distinguished (CDG-I; endoplasmatic reticulum and CDG-II; Golgi apparatus). Liver involvement is frequent in both groups and can even be predominant for some CDG-II variants. Abnormal glycosylation is seen in liver cirrhosis, probably resulting from affected liver synthesis. We hypothesized that mass spectrometry (MS) differentiates between secondary and bonafide genetic causes in end-stage liver disease.

AIMS & METHODS: To determine the effect of a diminished liver function on glycosylation we analyzed anonymous serum samples drawn from end-stage liver disease patients prior to their liver transplantation. As a first step we used transferrin isoelectric focusing (tIEF) to detect abnormal glycosylation. Selected samples were further analyzed with transferrin whole-protein MS to obtain a comprehensive readout of the glycosylation profile.

We also obtained serum from 100 patients with a presumed CDG. Patients with a predominant liver phenotype were selected for further analysis using exome sequencing for identification of the pathogenic mutation.

RESULTS: We collected 1065 serum samples and found an abnormal tIEF pattern in 30%. All abnormalities were mild and resembled a CDG-II pattern. MS of abnormal tIEF samples had increased fucosylation of transferrin and loss of one sialic acid.

We identified 18 patients with a phenotype resembling Wilson disease with liver fibrosis, elevated transaminases, low ceruloplasmin and liver copper accumulation. DNA is currently prioritized for exome sequencing. MS comparison of the Wilson disease-like patients and liver transplant patients showed that desialization is more abundant in Wilson disease-like patients and transferrin fucosylation is seen more often in liver transplant patients.

CONCLUSION: Whole protein MS enables differentiation between abnormal glycosylation secondary to liver failure and bonafide CDG. This can aid in the detection of CDG as a cause for liver pathology.

Disclosure of Interest: None declared

P0016 MICRORNA EXPRESSION PROFILE IN SIMPLE STEATOSIS AND NON-ALCOHOLIC STEATOHEPATITIS

K. Okamoto1,*, T. Okamoto1, T. Onoyama1, K. Miyoshi1, M. Kishina1, J. Kato1, S. Tokunaga1, T. Sugihara1, Y. Hara2, M. Koda1, K. Hino2, Y. Murawaki1

12nd. Dept. of Internal Medicine, Tottori Univ. School of Medicine, Yonago, 2Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are regarded as histological subtypes of non-alcoholic fatty liver disease (NAFLD). The distinctive pathological difference between SS and NASH is that NASH induces chronic liver inflammation and fibrogenesis, which can lead to liver cirrhosis. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression by repressing translation or degrading target mRNAs. Accumulating evidence indicates that miRNAs play important roles in various life functions including inflammation, metabolism, and fibrosis.

AIMS & METHODS: The purpose of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans. DD Shionogi (DS), Fatty Liver Shionogi (FLS), and FLS ob/ob mice were subjected as the normal control, SS model, and NASH model, respectively. Microarray analysis was used to assess 375 miRNA expression profiles in mouse liver tissue. Normalized miRNA expression ratios over ±2log2 between FLS and FLS ob/ob were identified as candidates. Real time PCR was used to check the reproducibility of the microarrays predicting miRNAs from 4 mice in each group. The putative miRNA target genes were predicted using the web-driven software DIANA microT-CDS. DAVID 6.7 was used to perform gene ontology annotation and KEGG pathway enrichment analysis. The putative miRNA expression profiles in human serum were also examined in every 10 patients with asymptomatic gallbladder stones, SS, and NASH.

RESULTS: In microarray analysis, 18 miRNAs were identified as candidates. Among the 18 miRNAs, 6 showed good expression ratio reproducibility in real time PCR and were confirmed to express commonly between mice and humans. The expression levels of miR-200a and miR-200b increased in the order of normal control, SS, and NASH. miR-1 was downregulated in NASH. miR-376c, miR-409, and miR-411 showed potent high expression in SS, over 30-fold of DS. KEGG pathway analysis indicated that the strongly expressed miRNAs in SS (miR-376c, miR-409, and miR-411) had multiple targets in the TGF-β signaling pathway including TGFR, smad 2, 3, and 4. The analysis suggests that miR-376c, miR-409, and miR-411 may protect liver fibrosis through silencing the TGF-β signaling pathway. In human serum, hierarchical clustering analysis of the putative miRNA expression also showed clearly different expression profiles between SS and NASH.

CONCLUSION: The expression profiles of 6 miRNAs were different between SS and NASH models. Some potential target genes of the putative miRNAs were found to be involved in the TGF-β signaling pathway. Furthermore, the putative miRNA expression profiles in human serum were also clearly different between SS and NASH patients. These miRNAs have high potential as biomarkers to distinguish the fate of NAFLD patients and contribute to further research in the pathogenesis and treatment of NASH.

Disclosure of Interest: None declared

P0017 PROTECTIVE EFFECTS OF MELATONIN ON THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS

K. Celinski1,*, G. Czechowska 1, A. Korolczuk2, G. Wójcicka3, J. Dudka4, A. Bojarska-Junak5, A. Mądro1, H. Cichoż-Lach1

1Gastroenterology, 2Department of Clinical Pathomorphology, 3Department of Clinical Pathophysiology, 4Medical Biology, 5Clinical Immunology, MEDICAL UNIVERSITY OF LUBLIN, Lublin, Poland

Contact E-mail Address:[email protected]

INTRODUCTION: The aim of the present study was to determine the effect of melatonin on liver fibrosis induced with long-term administration of thioacetamide (TAA) in an animal model. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis, i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and direct markers represented by proinflammatory cytokines such as interleukin 6 (IL-6), interleukin beta 1 (IL-beta1), tumour necrosis factor alpha (TNF-alpha, transforming growth factor beta 1 (TGF-beta1) and platelet-derived growth factor (PDGF- AB). Moreover, parameters of oxidative stress were determined, i.e. concentrations of oxidised glutathione (GSSG) and reduced glutathione (GSH), activity of paraoxonase 1 (PON-1), an enzyme of antioxidative properties. Inflammatory changes and extent of fibrosis were evaluated histologically.

AIMS & METHODS: Experiments were carried out in Wistar rats. Animals were divided into 4 groups, 8 individuals each: group I- controls receiving drinking water ad libitum for 12 weeks, group II – TAA, 300 mg/L ad libitum for 12 weeks, group III- melatonin, 10 mg/kg b.w. administered intraperitoneally (IP) daily for 4 weeks, group IV – TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. administered IP daily for 4 weeks.

RESULTS: Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin (IV) compared to the group receiving only TAA (II). Immunoenzymatic findings regarding the effect of melatonin on concentration of proinflammatory cytokines (Il-6, Il-beta1, TNF-alpha, TGF-beta 1, PDGF-AB) confirmed these data.

CONCLUSION: Biochemical examinations in liver homogenates revealed statistically significant improvement of oxidative stress parameters (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin (IV). Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was found to be increased in liver homogenates and serum in the group receiving TAA followed by melatonin (IV) compared to the TAA group (II). Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

Disclosure of Interest: None declared

P0018 ROLE OF GAMMA-KETOALDEHYDES AS NOVEL MEDIATORS OF EXPERIMENTAL FIBROGENESIS AND STELLATE CELLS ACTIVATION

L. Longato1,*, K. Rombouts1, D. Dhar1, S. Davies2, J. Roberts2, T. V. Luong1, M. Pinzani1, K. Moore1

1UCL Institute for Liver & Digestive Health, University College London, London, United Kingdom, 2Pharmacology, Vanderbilt University, Nashville, United States

Contact E-mail Address:[email protected]

INTRODUCTION: Reactive lipid aldehydes formed during lipid oxidation such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSCs) to a pro-fibrogenic phenotype. γ-Ketoaldehydes (γ-KAs) are highly reactive lipid aldehydes formed during oxidation of arachidonic acid or as a by-product of the cyclo-oxygenase pathway. γ-Ketoaldehydes are ∼100x more reactive than HNE, and form protein adducts and cross-links. Increased circulating concentrations of proteins cross-linked to γ-ketoaldehydes are present in patients with alcoholic liver disease.

AIMS & METHODS: The aim of this study was to investigate whether one specific γ-ketoaldehyde, namely levuglandin E2 (LGE2), can induce activation of HSCs. Cultured activated, serum-starved primary mouse and human HSCs were exposed to various concentrations (0.5 pM-5 µM) of levuglandin E2 (LGE2) for up to 48 hours. Endpoints measured included proliferation (BrdU incorporation), cytotoxicity (lactate dehydrogenase (LDH) release and tetrazolium (MTS) reduction), RNA expression (qRT-PCR), protein expression (Western Blot), and collagen secretion in conditioned medium (SirCol assay).

RESULTS: HSCs exposed to LGE2 exhibited profound cytotoxicity at 5 μM concentration, as indicated by LDH leakage and reduced MTS. This was mediated by an induction of apoptosis, indicated by an increase in PARP cleavage, occurring as early as 8 hours after LGE2 exposure. However, at lower, non-cytotoxic doses (ranging from 50 pM-500 nM, with a maximum effect observed at 0.5 nM), LGE2 promoted HSC activation as indicated by increased expression of α-smooth muscle actin and vimentin, as well as increased proliferation and collagen secretion. In addition, LGE2 exposure promoted sustained activation of signalling pathways, as indicated by the increased phosphorylation of the kinases ERK1/2 and JNK, as well as an increase in mRNA levels of chemokines such as IL-8 and MCP-1. We are currently investigating the potential protective action of administration of a γ-ketoaldehyde scavenger in an animal model of hepatic fibrosis.

CONCLUSION: γ-Ketoaldehydes represent a newly identified class of activators of HSCs in vitro, which are biologically active at concentrations as low as 50 pM.

Disclosure of Interest: None declared

P0019 NONINVASIVE SERUM FIBROSIS MARKERS IN COMPARISON WITH GRADING AND STAGING IN CHRONIC HEPATITIS

M. Abdollahi1,*, A. Pouri2, M. Somi2

1Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, 2Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Islamic Republic Of

Contact E-mail Address:[email protected]

INTRODUCTION: Chronic hepatitis is defined as a necroinflammatory disease of the liver continuing for at least six months. The aim of this study was to evaluate the role of noninvasive fibrosis markers by assessing the association among grading and staging and these diagnostic parameters in patients with chronic hepatitis.

AIMS & METHODS: We retrospectively studied 221 patients with chronic hepatitis between 2011 and 2013. Routine biochemical indices and serum fibrosis indexes such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were determined, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Receiver operating characteristic curve (ROC) analysis was conducted to compare diagnostic accuracies of these markers for prediction of significant fibrosis.

RESULTS: We identified 221 liver biopsies from chronic hepatitis patients with contemporaneous laboratory values for imputing AAR, APRI and FIB-4. From all, 135 males (61.1%) and 86 females (38.9%), with the mean age of 39.6±14.4 were studied. FIB-4, APRI and AAR were correlated significantly with the stage of fibrosis, with a higher correlation coefficient than other markers in the patients with Hepatitis B (r =  0.46), C (r =  0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) was superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy.

CONCLUSION: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Disclosure of Interest: None declared

P0020 REVEALING THE MOLECULAR MECHANISM OF RAT LIVER RESPONSE TO LONG-TERM OMEPRAZOLE TREATMENT WITH BIOINFORMATICS APPROACH

S. Vakal1, E.A. Virag2, K. Dvorshchenko1, L. Ostapchenko1,*

1ESC "Institute of Biology", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, 2University of Pecs, Pecs, Hungary

Contact E-mail Address:[email protected]

INTRODUCTION: Omeprazole is a widely prescribed acid-suppressing drug available for clinical use for 25 years. Despite well-studied adverse effects of short-term omeprazole treatment, underlying mechanisms of some hepatotoxic effects of long-term injection of high omeprazole doses (e.g. development of oxidative stress and histopathologic changes [1]) are not understood. Transcriptome analysis is a powerful tool for elucidation of possible mechanisms of cellular response to different conditions on molecular level. Bioinformatics approach is suitable for processing of large datasets, prediction of possible regulatory circuits and generation of hypotheses on involved molecular mechanisms [2].

AIMS & METHODS: The purpose of the research was to find out possible molecular mechanisms of rat liver cells response to long-term injection of omeprazole.

GSE8858 dataset and GPL2454 platform description were downloaded from NCBI Genome Expression Omnibus database. Gene expression data from livers of rats treated with 30 mg/kg and 415 mg/kg for 1 and 25 days were compared in order to reveal differentially expressed genes (DEGs). DEGs were determined with GEO2R tool on the basis of t-criterion and adjusted p value. Gene ontology (GO), pathway enrichment analyses and building of protein-protein interactions (PPI) network were performed with STRING 9.1. Prediction of miRNAs and cis-elements for DEGs was carried out with WebGestalt toolkit. Clusters were identified by K-means analysis in ClusterONE. All networks were visualized using Cytoscape.

RESULTS: In total 79 DEGs (21 up- and 58 down-regulated) and 87 DEGs (41 up- and 46 down-regulated) were identified in samples of rat livers treated with 30 and 415 mg/kg during 25 days, respectively. At the same time 22 genes with similar pattern of expression (9 up- and 13 down-regulated) were found for both types of dosage. Among them are Arntl, Cdk1a, Chka, Gpam, Litaf, Slc2a5, Usp2 etc. Enrichment in such GO terms was revealed: cell cycle, mitosis, nuclear division, lipid metabolism. Only genes involved in lipid metabolism were up-regulated, while others were suppressed. Genes involved in PPAR signalling pathway were found to be differentially regulated upon 25-day treatment with omeprazole. Most of DEGs (51 genes) were of cytoplasmic proteins (housekeeping genes). PPI networks were constructed for 98 proteins and 102 interactions revealed. The optimal amount of clusters was equal to 3. MiRNA-9, 17-5p, 20A, 20B, 106A, 106B, 200B, 200C, 429, 506 and 519D were found to be involved in regulation of revealed DEGs. 24 probable cis-elements were predicted for promotors of identified DEGs.

CONCLUSION: Thus, long-term treatment of rats with omeprazole is associated with changes in expression of housekeeping genes: down-regulation of genes involved in cell-cycle process and cellular division, up-regulation of genes involved in lipid metabolism, and changes in expression of PPAR signalling pathway genes.

REFERENCES

1. Dvorshchenko KO, Bernyk OO, Dranytsyna AS, et al. Influence of oxidative stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term gastric hypochlorhydria and administration of multiprobiotic Symbiter. Ukr Biokhim Zh 2014; 85: 114-123.

2. Shen B, Zhou S, He Y, et al. Revealing the underlying mechanism of ischemia reperfusion injury using bioinformatics approach. Kidney Blood Press Res 2013; 38: 99-108.

Disclosure of Interest: None declared

P0021 MORPHOLOGICAL AND FUNCTIONAL CHANGES OF LIVER MACROPHAGES DURING THE PROGRESSION OF NONALCOHOLIC STEATOHEPATITIS (NASH)

S. Bruzzi'1,*, S. Sutti1, A. Jindal1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1

1Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Recent reports indicate that both human and experimental NASH is characterized by an increase in hepatic monocyte infiltration and that macrophages have an important role in regulating the disease evolution. However, little is known about the functional changes occurring in liver macrophages during the progression of NASH.

AIMS & METHODS: NASH was induced in C57BL/6 mice by feeding a methionine-choline deficient (MCD) diet up to 8 weeks.

RESULTS: Mice receiving the MCD diet showed a progressive worsening of parenchymal damage and lobular inflammation, while liver fibrosis was evident only after 8 weeks of treatment. Hepatic F4/80-positive macrophages increased in parallel with the disease progression. In the early phases of NASH after 4 weeks on the MCD diet these cells prevalently expressed markers of inflammatory monocytes such as Ly6C and CD11b, but the prevalence of Ly6C+/CD11b+ cells decreased by extending the treatment up to 8 weeks. This paralleled with a lowering in the monocyte chemokines CCL1/CCL2 and their receptors CCR8/CCR2. We observed that the expression of the macrophage M1 activation markers iNOS and IL-12 also peaked at 4 weeks and declined thereafter. No appreciable changes were instead observed in the levels of M2 polarization markers arginase-1 and MGL-1. Histology revealed that the macrophages accumulating in advanced NASH (8 weeks MCD) were enlarged, vacuolized and formed small aggregates. Immunofluorencesce showed that these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting that they have phagocytosed apoptotic bodies derived from dying fat-laden hepatocytes. At flow cytometry, enlarged macrophages were characterized by a weak Ly6C/CD11b expression and by a low IL-12 production. On the other hand, these cells showed an enhanced expression of the anti-inflammatory mediators IL-10 and annexin A1. The production of the pro-fibrogenic cytokine TGF-β was increased in the macrophages obtained from NASH livers, irrespective of the cell phenotype.

CONCLUSION: Altogether, these data indicate that during the progression of NASH liver macrophages down-modulate their pro-inflammatory phenotype in parallel with the phagocytosis of apoptotic hepatocytes and acquired anti-inflammatory properties.

This work has been supported by a grant from the Fondazione Cariplo (Milan).

Disclosure of Interest: None declared

P0022 MICRORNA-27B DEVELOP THE FATTY LIVER FORMATION AND INSULIN RESISTANCE AT THE SAME ONSET

T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, Y. Eguchi2, K. Wada3, A. Nakajima1

1gastroenterology and hepatology, Yokohama city university, yokohama, 2internal medicine, saga university, saga, 3 Pharmacology, Osaka University Graduate School of Dentistry, Oosaka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in Asia Pacific region is close to 12–24%, while in Western countries is about 20–30%1). And nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. In spite of its high prevalence, up till now there is no proven effective treatment for NAFLD3). Along with the “obesity epidemic,” the worldwide prevalence of NAFLD is increasing rapidly and is generally assumed to be a consequence of obesity-induced insulin resistance 2). On the other hand, not all obese individuals are insulin resistant, nor are all insulin-resistant individuals obese 4). MicroRNAs (miRs) are a class of small non-coding RNAs that function to control gene expression by inducing the degradation or inhibiting the translation of mRNA through an association with its 3’-untranslated region (3’UTR). Although miRs play a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM), detailed mechanisms of this pathogenesis remain unclear.

AIMS & METHODS: We found that miR-27b increased in liver biopsy specimens of NAFLD patients with DM using microarray analysis, as compared with controls. The aim of this study was to investigate whether overexpression of miR-27b in liver could cause fatty liver formation and insulin resistance, and to examine the mechanism of NAFLD and DM onset in a murine model.

Five-week-old male C57BL/6J mice were randomized into 2 groups (n = 16 mice): basal diet (BD)-fed control mimic (BD-Con, n = 4), BD-fed miR-27b-mimic (BD-miR-27b, n = 4). In this study, miR-27b mimic is injected intravenously at 7mg/kg. We comfirmed the target genes of miR-27b using quantitative RT-PCR analysis. Insulin serum concentrations were measured by a local laboratory for clinical examinations. As an alternative method for assessing insulin resistance (IR), the homeostasis model assessment of IR (HOMA-IR) was calculated using the following formula: fasting insulin (mU/mL) plasma glucose (mg/dL) / 405.

RESULTS: BD-miR-27b significantly showed steatosis using oil red o staining and increased hepatic tryglyceride content, as compared with BD-Con. In the analysis of fat accumulation-related gene expression, hepatic Peroxisome proliferator-activated receptor α (PPARα) and Microsomal triglyceride transfer protein (MTTP) are significantly decreased. At the same time, BD-miR-27b showed hyperinsulinemia and insulin resistance. In the analysis of insulin resistance-related gene expression, hepatic Insulin receptor substrate 1 (IRS-1) is significantly decreased.

CONCLUSION: miR-27b controls multiple gene levels that are involved in fat accumulation and insulin resistance, resulting in the NAFL and DM pathology. These results propose a therapeutic approach for NAFL and DM by targeting miR-27b.

REFERENCES

1) Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia–Pacific region: executive summary. J Gastroenterol Hepatol 2007; 22: 775–777.

2) Clark JM, Brancati FL and Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649–1657.

4) Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity: European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166–1173.

Disclosure of Interest: None declared

P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER REGENERATION IN A RABBIT MODEL

F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van Gulik1

1Surgery, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase future remnant liver volume in patients requiring extended resections. Reversible PVE is of interest when generating sufficient hypertrophy while preserving the embolized liver lobe. The concept of reversible PVE requires an absorbable embolization material.

AIMS & METHODS: The aim of this study is to modulate lysis time of a fibrin-glue based embolization material while using different concentrations of Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG.

PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5 groups:

• Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), n = 4)

• Fibrin glue with Aprotinin (FG700KIU, n = 5)

• Fibrin glue with Aprotinin (FG500KIU, n = 5)

• Fibrin glue with Aprotinin (FG300KIU, n = 5)

• Fibrin glue without Aprotinin (FG-Aprot, n = 5)

The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight ratio of NEL were evaluated.

RESULTS: Data were compared with a previous series using a permanent embolization material, i.e. polyvinyl alcohol + coils (PVAc), showing complete and permanent occlusion of the embolized portal vein branch in all rabbits after 7 days.

FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of the FG+1000KIU Aprotinin group was still occluded and showed a hypertrophy response comparable to the PVAc group. The group of FG 700KIU Aprotinin survived 14 days and in two of the five rabbits, the embolized portal vein was recanalized at sacrifice. The hypertrophy response in these rabbits was not different from the PVAc group. The rabbits with FG 500KIU and 300KIU Aprotinin were sacrificed at day 49. In the group with FG 500KIU Aprotinin, 4 out of 5 showed recanalization of the cranial portal branches. In the group with FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups showed hypertrophy response rates not different compared to the PVAc group.

CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU Aprotinin resulted in 70% reversible embolization with a hypertrophy response comparable to the PVAc group.

Disclosure of Interest: None declared

P0024 TRANSPLANTATION OF HUMAN AMNION-DERIVED MESENCHYMAL STEM CELLS AMELIORATES CARBON TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS

K. Kubo1,*, S. Ohnishi1, N. Sakamoto1

1Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease caused by a variety of factors, such as viral infections, alcohol, drugs and chemical toxicity. The only effective available treatment for end stage liver fibrosis is transplantation; however, due to the lack of donors, complications and transplant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs) have been reported to be a valuable cell source in cell therapy. Recently, bone marrow- or adipose tissue-derived MSCs have been reported to be effective in the treatment of liver fibrosis. In addition, several studies have shown that MSCs can be easily isolated from human amnion, and a large amount of cells can be obtained. Therefore, we examined the effects of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.

AIMS & METHODS: All pregnant women gave written informed consent, and amnion was obtained at Cesarean delivery. hAMSCs were isolated by collagenase treatment, and expanded with culture medium containing fetal bovine serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a week for 7 weeks. At 3 weeks, hAMSCs (1×106 cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative RT-PCR were performed.

RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area and deposition of type I collagen. In addition, hAMSC transplantation significantly decreased the number of α-SMA-positive hepatic stellite cells and and CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expression of α-SMA was significantly decreased in the liver of hAMSC-treated rats, and mRNA expression of type I collagen, TGF-β and IL-1β tended to be decreased by hAMSC transplantation.

CONCLUSION: Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through inhibition of inflammatory reaction. hAMSC would be considered as a new cell source for the treatment of liver fibrosis.

Disclosure of Interest: None declared

P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER CELLS IN AN ANIMAL MODEL OF NAFLD

V. Lembo1,*, G. Mazzone1, G. D'Argenio1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine and Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most common liver disease in Western countries, is pathogenetically related to a sedentary lifestyle as well as to poor quality diet characterized by an excessive energy intake including high fatty foods and high amounts of fructose, the so-called Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of triglycerides. Vitamin D in addition to the effects on lipid metabolism, plays other biological functions, among which a trophic effect on human cultured cells.

AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by Western Diet, the relationship between body weight, liver weight and grade of steatosis; and if these parameters are modified by vitamin D supplementation. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD); WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment was conducted for 6 months. Weekly, the rats, body weight was recorded. At sacrifice, livers were excised and weighed and samples were stored at -80°C. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis was numerically scored following semi-quantitative pathological standard.

RESULTS: During the experiment the increase of body weight was similar in the three groups. In the two groups fed with WD liver weight was significantly higher than SD group (p<0.01). A positive correlation between body weight and liver weight was observed in WD groups (p<0.0001). The liver/body weight ratio was significantly higher in WD and WDVitD groups than SD: 2.9±0.05, 2.8±0.07 and 2.0±0.04, respectively; p<0.001). Steatosis was present in 61% and 21% of hepatocytes in WD group and WDVitD group, respectively, and absent in SD group. No correlation was found between the grade of steatosis and liver or body weight nor between the grade of steatosis and liver/body weight ratio. Although vitamin D supplementation reduced the degree of steatosis, liver/body weight ratio in WDVitD group was similar to WD group.

CONCLUSION: In a rat model of NAFLD induced by WD the presence and extent of steatosis are independent from body weight. Interestingly and unexpectedly, in WD groups the supplementation with vitamin D reduces liver steatosis but not liver weight: this sustains the hypothesis of a trophic effect of vitamin D on liver cells.

Disclosure of Interest: None declared

P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT MODEL OF NAFL

G. Mazzone1,*, V. Lembo1, G. D'Argenio1, M. Guarino1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine and Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease (NAFLD) rise to become the most common cause of chronic liver disease in Western countries. It is known that insulin resistance and type 2 diabetes mellitus (T2DM) have an important role in the pathogenesis of obesity and NAFLD. A growing body of evidence points to a linked and potentially causative relationship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.

AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin D3 supplementation is able to modulate the liver effects and glucose homeostasis of a westernized diet, high in fat and fructose, in an animal model of NAFL without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23 IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6 months. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Insulin resistance was determined according to the Homeostasis Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evaluated according to Brunt EM et al.

RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while in WDVitD group only 27% of hepatocytes contained fat. In WD group HOMA-IR was significantly higher than in SD (41.9±8.9 vs 6.17±1.3, p<0.01) and it was reduced by vitamin D supplementation in WDVitD group (41.9±8.9 vs 19.4±5.2, p<0.05). Interestingly SD and WDVitD rats were not diabetic (98.7±8.0 and 103.2±6.1, respectively) while all rats in WD group were diabetic (139±9.6) with glycemic values significantly higher than SD (p<0.01) and WDVitD (p<0.05).

CONCLUSION: These results suggest that a daily supplementation of vitamin D3 is able to improve insulin sensitivity and to prevent the development of diabetes and hepatic steatosis in WD rats.

Disclosure of Interest: None declared

P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE

S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3, H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1

1Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research Center for Post-genome Science and Technology, 4Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Sphingomyelin (SM) is a major component in lipid microdomains, and SM is synthesized from ceramide by the action of SM synthase (SMS). We have recently reported that mice deficient for SMS2 are resistant to high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem 2011:286;28544). In this study, we examined the relationship between SM and ceramide molecular species and the development of NAFLD and insulin resistance in human.

AIMS & METHODS: Non-alcoholic students of our university with body mass index (BMI) ≥ 35 kg/m2 at the regular physical checkup in 2013 were enrolled, and volunteer students with BMI of 20-22 kg/m2 were set as a control group. Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0, C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver enzymes, lipids and insulin resistance were measured by blood examination. Abdominal ultrasound was performed to confirm the existence of fatty liver, and body composition including percent body fat (PBF) was measured by bioimpedance analysis.

RESULTS: The levels of total SM and ceramide were not altered in obese group (19-28 y.o., n = 12), compared with control group (18-27 y.o., n = 11). The concentrations of SM C18:0 and C24:0 in the obesity group were significantly higher than in the control group. Moreover, in the obese group, SM C20:0 and C22:0 tended to be higher than in the control group. In the analysis of total 23 cases, the serum levels of SM containing saturated fatty acids positively correlated with PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing unsaturated acyl chain and almost all ceramide species did not correlate with those items.

CONCLUSION: The present study demonstrated that the serum levels of SM species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are correlated with liver function and insulin resistance, suggesting that distinct SM species are involved in the development of NAFLD and insulin resistance.

Disclosure of Interest: None declared

P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18 AND CONTROLLED ATTENUATION PARAMETER (CAP) IN HEALTHY POPULATION

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutrição e metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative for the diagnosis of NAFLD, especially NASH.

AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy individuals with and without steatosis. Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis compared with US and CAP was assessed using AUROC.

RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass index) were 52.6±17.1 years and 28.2±4.9 kg/m2, respectively; 25% had a normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis on ultrasound was 52.1%.

The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respectively. Median CK-18 were elevated in patients with vs. without hepatic steatosis by ultrasound: 33.4 [IQR: 25–151] vs. 73.7 [IQR: 25–508] U/L, p <0.0001.

CK-18 significantly correlated with steatosis (ρ = 0.40), ALT (ρ = 0.40), CAP (ρ = 0.38), triglyceride (ρ = 0.32), waist circumference (ρ = 0.30), HDL (ρ = -0.28), AST (ρ = 0.27), LDL (ρ = 0.26), total cholesterol (ρ = 0.21) and the number of metabolic syndrome criteria (ρ = 0.29), but not with LSM or BMI.

The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of 243 dB/m) were 0.78 (95% CI = 0.71–0.86) and 0.74 (95% CI = 0.65–0.82), respectively.

CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151, with a very large range. It showed a good discriminating capacity for diagnosing steatosis.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI) AND ULTRASOUND

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, A. Carvalho3, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

INTRODUCTION: The fatty liver index (FLI) derived from an Italian population includes serum triglycerides, serum gamma-glutamyltransferase, body mass index (BMI) and waist circumference. It has been used as a noninvasive measure of hepatic steatosis (HS), but has not been widely validated and not examined in the Portuguese population.

AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult population by fatty liver index (FLI) and correlate with the ultrasound findings; validate FLI for prediction of fatty liver in the Portuguese population.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI. Performance of FLI for diagnosing steatosis compared with US was assessed using AUROC.

RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circumference and BMIs were 50.5±18.4 years, 94.4±12.7 cm and 26.9±4.7 kg/m2, respectively; 43% were overweight and 22% were obese. The median of FLI was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.

Using the FLI, 27.6% of subjects had HS (FLI > 60), 41.8% had no HS (FLI < 30) and 30.6% were not classifiable (FLI 30-60). However, these cut-offs proposed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI <30 exhibited HS on ultrasound and 13.4% of subjects with FLI > 60 showed no steatosis. For the FLI, the area under the ROC curve was 0.88 for the diagnosis of HS.

There was a significant correlation (p < 0.01) between the FLI and the following variables: weight (ρ = 0.80), waist circumference (ρ = 0.74), presence of steatosis (ρ = 0.65), triglycerides (ρ = 0.58), BMI (ρ = 0.51), ALT (ρ = 0.43), GGT (ρ = 0.39), HDL (ρ = -0.36), age (ρ = 0.33), female sex (ρ = -0.33), insulin (ρ = 0.29), AST (ρ = 0.28), LDL (ρ = 0.24) and total cholesterol (ρ = 0.22). No correlation was found with physical activity.

CONCLUSION: FLI could accurately identify hepatic steatosis in the general Portuguese population. The calculation of FLI may be useful to suggest the possibility of the presence of steatosis and indicate the need for an abdominal ultrasound.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0030 “NORMAL” CONTROLLED ATTENUATION PARAMETER (CAP) VALUES: A POPULATION-BASED STUDY OF HEALTHY SUBJECTS

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. The normal range of controlled CAP values needs to be explored in clinical and anthropometrically diverse healthy subjects. A recent study has shown an association of CAP with BMI and the number of metabolic syndrome criteria.

AIMS & METHODS: Aim: define the normal range of CAP values in healthy subjects and evaluate the associated factors.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. CAP was performed using Fibroscan in 134 healthy subjects, without fatty liver on ultrasonography or positivity serology for HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.

RESULTS: From 134 consecutive individuals studied (66 males), 4 were excluded due to failure/unreliable liver stiffness measurements (LSM). The mean age and BMIs (body mass index) were 46.9±18.0 years and 24.9±3.5 kg/m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were obese. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3 dB/m, respectively. Men had a higher mean CAP value than women (mean±SD: 213.1±47.1 dB/m versus 191.8±47.8 dB/m, respectively; p = 0.012).

CAP significantly correlated with gender (ρ = 0.22), age (ρ = 0.22), waist circumference (ρ = 0.33), BMI (ρ = 0.22), alcohol consumption (ρ = 0.25), systolic blood pressure (ρ = 0.27), ALT (ρ = 0.27), fasting glucose (ρ = 0.24) and the number of metabolic syndrome criteria.

After allowance for potential confounders, CAP was not independently associated with BMI or other risk factors for nonalcoholic fatty liver disease.

CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy subjects and is not associated with BMI or the number of metabolic syndrome criteria.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL

T.J. G. Gevers1,*, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4, J.P. Drenth1

1Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology, 4Nephrology, RadboudUMC, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Several trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and possibly enhances risk for adverse events.

AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial) was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We excluded patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2. Primary outcome was change in liver volume, secondary outcomes were changes in kidney volume, eGFR, symptom relief and health-related quality of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within-group differences.

RESULTS: We included 43 ADPKD patients with polycystic liver disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver volume decreased from 4,859 ml to 4.595 ml (-3.1%;p<0.001), and median kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p = 0.006). eGFR declined 3.5% after the first injection and remained stable up to study end. Lanreotide significantly relieved postprandial fullness, shortness of breath and abdominal distension, but had no effect on any of the EuroQol-5D dimensions. Three participants had a suspected episode of hepatic or renal cyst infection during the study.

CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting lanreotide, but stabilized thereafter.

Disclosure of Interest: None declared

P0032 THE EFFECTS OF POLY-UNSATURATED FATTY ACIDS (PUFAS) IN A RODENT NUTRITIONAL MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)

V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1

14th Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

INTRODUCTION: NAFLD and subsequent NASH are probably the most common chronic liver diseases in western countries and have a high risk of development of liver cirrhosis associated with high morbidity and mortality.

AIMS & METHODS: The aim of the study was to determine effects of administration of PUFAs in the MCD dietary model of NASH and to assess the potential anti-inflammatory role of PUFAs in the pathogenesis of NASH.

For 6 weeks were male mice fed either with MCD or with chow. There were 4 groups of animals. Both experimental and control groups received from the beginning either PUFAs or saline. Detailed liver histology, serum biochemistry, total lipid and fatty acids compound, adiponectin and leptin levels were determined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were measured.

RESULTS: Feeding with MCD resulted in histopathological changes of NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP). Administration of PUFAs led to significant decreases of total animal and liver weight in MP. PUFAs also decreased cholesterol levels (P<0.001), ALT (P<0.01) and AST levels (P<0.01). MP developed significantly less pro-inflammatory cytokine profile, had lower leptin (P<0.01) and higher adiponectin levels (P<0.01) than controls. Administration of PUFA led also to lower serum concentrations of saturated and monounsaturated FA and to higher serum concentrations of polyunsaturated FA in MP. Total lipid content of liver was significantly lower in MP.

CONCLUSION: We conclude that PUFAs may play a causal role in the pathophysiology of NASH. In summary, PUFAs have favorable effects on histopathological changes, serum markers of liver damage, fatty acid compound and show anti-inflammatory properties. We expect that PUFAs may represent a promising way in prevention and treatment of this increasingly common disorder.

Disclosure of Interest: None declared

P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

W. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1, Y. Liu1,*

1Department of Gastroenterology, 2Institute of Clinical Molecular Biology & Central Laboratory, Peking University People's Hospital, Beijing, China

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by a broad spectrum of hepatic pathology that is closely linked to obesity and ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and even cirrhosis. NAFLD is recently believed to be under the influence of the gut microbiota, which may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein.

AIMS & METHODS: We explored the composition of gut bacterial communities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina next-generation sequencing.

RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that most of the microbiota samples were clustered by disease status. Differences were abundant at phylum, family, and genus levels between NAFLD and healthy subjects. Lentisphaerae at phylum level was significant higher in NAFLD microbiota. Among those taxa with greater than 0.1% average representation in all samples, five genera including Alistipes and Prevotella were the genus types exhibiting significant higher level in healthy microbiota, while genera Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in NAFLD microbiota. In addition, lymphocyte profiles (CD4+T cell and CD8+T cell) and proinflammatory cytokines (TNF-α, IL-6 and IFN-γ) in gut biopsies of patients and healthy controls was analyzed to monitor the inflammation caused by dysbiosis microbiota. The levels of CD4+ T cells and CD8+ T cells were lower in NAFLD patients compared with healthy subjects, and the proinflammation cytokine TNF-α, IL-6 and IFN-γ showed high level in NAFLD patients. What was more, irregular arrangements of microvilli and widening of the tight junction were observed in gut mucosa of the NAFLD patients by transmission electron microscope.

CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD microbiota, decreased numbers of CD4+T cells and CD8+T cells, and increased levels of TNF-α, IL-6 and IFN-γ in gut mucosa of NAFLD patients suggest a role for gut microbiota in the gut inflammation and the dysregulated gut immunity, which promote pathogenesis of NAFLD. We postulate that the distinct composition of the gut microbiome among NAFLD and healthy controls could offer a target for intervention or a marker for disease.

REFERENCES

1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab 2013; 24: 537-545.

2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-127.

Disclosure of Interest: None declared

P0034 ASCITIC FLUID LACTOFERRIN FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS

A.A. Ghweil1,*

1TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY OF MEDICINE EGYPT, Qena, Egypt

Contact E-mail Address:[email protected]

INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This procedure is operator-dependent and lysis of PMNs during transport to the laboratory may lead to false-negative results. Furthermore, ascitic fluid culture is insensitive and leads to delays in diagnosis. The aim of this study was to assess the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to identify a cut-off level that can be used for future development of a rapid bedside test.

AIMS & METHODS: Sixty ascites samples from cirrhotic patients were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC concentrations were determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or greater with or without a positive culture was used for diagnosis of SBP.

RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/mL; compared with non-SBP samples (median, 39 ng/mL P < .001). The sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%, respectively. The area under the receiver operating characteristic curve was 0.98. Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis

CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis.

Disclosure of Interest: None declared

P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS

C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D. I. Gheonea1, I. Rogoveanu1

1Gastroenterology, UMF CRAIOVA, Craiova, Romania

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex treatable malignancies as its management is dependent on the stage of the underlying condition – liver cirrhosis. An early diagnosis assures best curative chances, as liver resection or transplantation have good survival rates in the general population. Computer aided diagnostic and prognosis (CADP) models are currently being developed for a number of malignancies to help clinicians manage cases based on individual needs of the patients rather than general statistics.

AIMS & METHODS: Our aim was to develop a CADP based on our previous work involving artificial neural networks (ANN) [1] for successfully diagnosing early HCC cases and better prognosticate their evolution, based on a set of criteria in accordance with current guidelines.

Ethical clearance was obtained from the local board and 107 consecutive patients with previously diagnosed liver cirrhosis signed informed consents for entering the study, between January 2009 and February 2010. Clinical and demographic parameters (age, sex, body mass index, waist circumference, type of viral infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein thrombosis, size and number of possible tumors), elastography data (strain ratio, complexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular second moment, correlation) and stiffness value (FibroScan) were collected and imputed in the CADP. For patients with clear liver tumors contrast-enhanced ultrasound was performed and time-intensity curve parameters were calculated and fed to the ANN system: peak enhancement, time to peak, rise time, fall time, mean transit time, area under the curve. We have followed the 4-year incidence of HCC patients in tumor-free cases and assessed the evolution when any formation, either regeneration nodule or early HCC was found.

RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules [median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm (min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per patient: 1 (min: 1, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration nodules based on clinical, laboratory and imaging data. A total of 28 patients also developed HCC in the four-year follow-up period; the system correctly predicted high possibility for HCC occurrence in 26 of these patients (92.85%), while giving high estimates for HCC in another 16 patients that remained cancer-free until now.

CONCLUSION: We could successfully predict the rate of malignancy in cirrhotic patients by using a novel CADP system. We believe that such tools may become worthy aids to clinical management of patients with various types of digestive pathologies.

REFERENCES

1. Streba CT, et al. Using contrast-enhanced ultrasonography time-intensity curves as classifiers in neural network diagnosis of focal liver lesions. World J Gastroenterol 2012; 18: 4427–4434.

Disclosure of Interest: None declared

P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE COHORT STUDY

F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4, B. Sean2

1Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, 2Intensive Care, 3Transplantation, University of Alberta, Edmonton, Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease (MELD) score ≥40 have high risk of death without liver transplant (LT). This study aimed to evaluate these patients’ outcomes after transplant.

AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic patients who underwent LT at one Canadian center between 2002 and 2012. Primary exposure was severity of end-stage liver disease measured by MELD score at transplant (≥40 vs. <40). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival rates.

RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score ≥40. These patients had longer first ICU stay after LT (14 vs. 2 days; p <0.001). MELD score ≥40 at transplant was independently associated with first ICU stay after transplant ≥10 days (OR, 3.21). These patients had longer first hospital stay after LT (45 vs. 18 days; p <0.001); however, there was no significant difference in the rate of ICU readmission (18% vs. 22%; p = 0.58) or re-transplant rate (4% vs. 4%; p = 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and 5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no significant difference in cumulative survival stratified by MELD score ≥40 vs. <40 at transplant (p = 0.59).

CONCLUSION: Cirrhotic patients with MELD score ≥40 at transplant utilize greater postoperative health resources; however, derive similar long-term survival benefit with LT.

REFERENCES

Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062.

Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation in patients achieving a model for end-stage liver disease score of 40 or higher. Transplantation 2013; 95: 507-512.

Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients. Crit Care 2010; 14: R117.

Disclosure of Interest: None declared

P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT STUDY

J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2, N. O'Connell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4

1Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust, Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI, University of Warwick, Coventry, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: There is a quest for biomarker discovery in liver disease especially to detect cirrhosis at an early stage. Current methods are invasive, more often requiring a liver biopsy to confirm the diagnosis. For patients with Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst generally helpful, is unable to confirm the presence of fibrosis particularly in the presence of fat within the liver which is inevitable in most cases with NASH.

The gut microbiome is altered in several gastrointestinal disorders, resulting in altered gut fermentation patterns, which we (and others) have been able to recognise by analysis of volatile organic compounds (VOC) in urine, breath and faeces1. The altered structure of the small intestinal mucosa and increased gut permeability (noted in liver disease), we hypothesised, would also change the microbiome, hence recognisable by its unique “fermentome” pattern, making NASH distinguishable from controls.

AIMS & METHODS: To determine if NASH results in an altered VOC pattern in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguishable from cirrhotics vs non-cirrhotics.

33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8 with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and 12 controls (normal synthetic liver function). Urine was collected and 10 ml aliquots were stored frozen in universal containers. For assay, the containers were first heated to 40 ± 0.1oC. The headspace (the air above the sample) was then pumped from the containers and analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used for initial statistical evaluation, with a re-classification using a “leave one out” for calculating sensitivity and specificity.

RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in these different groups of liver disease. The control group was significantly different to all of the other groups with a sensitivity of 100%. Of the disease groups, NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively with specificity of 80%. NAFLD however had sensitivity of 50% but specificity of 80%.

CONCLUSION: This pilot study suggests the IMS (FAIMS – technology) offers a novel non-invasive approach to separate not only NASH from controls but also those with established cirrhosis using urine. It offers the potential for early non-invasive tracking of NASH and its complications.

REFERENCES

1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Aliment Pharmacol Ther 2014; 39: 780-789.

Disclosure of Interest: None declared

P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES

N. Ding1,*

1Gastroenterology, St Vincent's Hospital, Melbourne, Australia

Contact E-mail Address:[email protected]

INTRODUCTION: Endoscopic screening for gastro-oesophageal varices (GOV) is currently recommended for all cirrhotic patients. Noninvasive methods for liver fibrosis assessment are identifying increasing numbers of patients with “cirrhosis-range” liver stiffness measurements (LSM), increasing the number of referrals for screening endoscopy. The identification of simple non-invasive markers for the presence/absence of large gastroesophageal varices (GOV) would be clinically useful. We evaluated the performance of liver stiffness measurement (LSM) ± platelet count to identify the presence of large GOV in patients with Child Pugh (CP) A cirrhosis.

AIMS & METHODS: Data were collected retrospectively. The presence of cirrhosis was defined by LSM > 13.6 kPa using elastography. We performed a database search for patients with LSM > 13.6 kPa who underwent screening gastroscopy (2010 – 2013). Only patients with compensated liver disease were included. Large GOV were defined by diameter > 5mm or the presence of high risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the combination of these factors to identify patients with large GOV. A training set of 71 patients was used, and results were validated using a second cohort of 201 patients from two independent centres.

RESULTS: The combination of LSM and Pl was more accurate for identifying CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs. 0.78 [0.66 – 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk score was 0.11 (Sens = 0.88, Spec = 0.77, PPV = 0.33, NPV = 0.98, accuracy = 78%). Results in the validation cohort confirmed the discriminatory power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically relevant cut-offs to improve the negative predictive value (NPV) for large GOV. The NPV for the combination of LSM < 25 kPa and Pl ≥ 100 and was 100% in both the training cohort and validation cohort. 82 (42%) of patients overall met this criteria.

CONCLUSION: The combination of LSM < 25 kPa and Pl ≥ 100 can be used to identify patients with compensated cirrhosis who do not have large GOV. These patients do not benefit from endoscopic screening, but could be followed with annual LSM and full blood count.

REFERENCES

1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 1997.

2. de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53: 762–768.

3. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144, 102–111.e1.

4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement using Fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164–170.

Disclosure of Interest: None declared

P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN LABEL STUDY DATA

C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1, E. Berni3, C.J. Currie1

1Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff, 2Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of cirrhosis. In recurrent, overt, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent episodes.

AIMS & METHODS: The aim of this study was to characterise the impact of the number of prior HE episodes on the risk of future HE episodes. A post-hoc analysis was carried out using data from 322 patients with a history of HE from a phase 3, open-label study evaluating the long-term safety and tolerability of rifaximin-α 550mg BID. All eligible patients had a Conn score of 0–2 at enrolment, and had either successfully participated in a previous HE study with rifaximin-α (RFHE3001), or they were new patients enrolled with ≥1 verifiable episode of HE within the preceding 12 months.

RESULTS: 319 of 322 patients (647 observations) aged ≥18 years had all the information required for analysis. Median duration of follow-up was 17 months (IQR 8.9–25.4). Stratifying patient observations by number of prior HE episodes and using the Kaplan Meier method the probability of being event free at year one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and 0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539 (0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for 'one', 'two', ‘three’ and ‘four or more' prior HE episodes, respectively. Plotting the Kaplan Meier curves of time to next HE episode, stratified by the number of prior HE episodes, a clear association between decreased time to next HE episode and increased number of prior episodes was seen. Using log-rank tests, there was no significant difference between the survival curves of one prior and two prior HE episodes (χ2 = 0 on 1 degree of freedom (d.f.), p = 0.899), however there were significant differences between survival curves of one prior or two prior episodes and greater numbers of prior episodes (χ2 = 72 on 3 d.f., p<0.001).

CONCLUSION: This study supports the current understanding of the natural history of end-stage encephalopathy; as the number of prior HE episodes increased, the risk of subsequent HE episodes increased.

Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other: Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni Consultancy for: Norgine, C. Currie Consultancy for: Norgine

P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION

P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1, J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on behalf of Vienna Hepatic Hemodynamic Lab

1Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

Contact E-mail Address:[email protected]

INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repeatable tool to assess liver fibrosis and portal hypertension (HVPG). Recently, new quality criteria for TE measurements have been proposed (Boursier et al. Hepatology 2013): very reliable: IQR/M <0.1; reliable: IQR 0.1–0.3, or IQR/M >0.3 if TE <7.1 kPa; poor reliable: IQR/M >0.3 if TE >7.1 kPa.

AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension. Therefore we retrospectively identified patients undergoing TE, HVPG measurement and liver biopsy within 3 months at our tertiary care center.

RESULTS: Among 278 patients (48.7±13.1 years, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R = 0.648 vs. R = 0.636) and HVPG (R = 0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively.

CONCLUSION: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

Disclosure of Interest: None declared

P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL ENDOSCOPY

S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernández-Sordo'1, J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1, I. N. Guha1

1Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham, UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical Catholic University of Chile, Santiago, Chile

INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD) remains the gold standard test to screen for oesophageal varices (OV) in patients with liver cirrhosis. However, it has many limitations in terms of costs, accessibility and tolerability. Hence, there is a need for less invasive and simple techniques to replace C-OGD in this setting.

AIMS & METHODS: We aimed to compare the accuracy and acceptability of a portable, disposable, office-based, unsedated transnasal video endoscope (EG Scan™ II) with C-OGD for the detection of OV.

This was a prospective diagnostic study. Consecutive adult patients with confirmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited to participate in this study. We excluded patients with recurrent epistaxis (more than once a week); nasal obstruction; disease of the nasal cavity; history of variceal bleeding or band ligation therapy in the past 12 weeks. All subjects underwent two procedures on the same day (EG Scan followed by C-OGD), performed by two different operators blinded to the findings of the other test. Patients completed validated tolerability (10-point visual analogue scale (VAS)) and adverse events questionnaires on day 0 and day 14.

The primary outcome measure was diagnostic accuracy of EG scan (performed by one operator) against C-OGD (reference standard). In addition, interobserver agreement of the EG scan was calculated using the kappa (k) statistic, by nine blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.

RESULTS: 50 patients were recruited to the study (mean age 59 years +/-11, 70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%) completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%), p = 0.882). OV prevalence was 48.9%.

Sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95% confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI 0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI 0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis of any size OV (K = 0.45, 95%CI 0.40-0.49) and medium/large OV (K = 0.47, 95%CI 0.42-0.52).

Patients reported better experience (mean VAS+/-standard deviation (SD)) and higher preference (percentage) with EG Scan compared to C-OGD at day 0 (7.8+/-2.2 vs. 6.8+/-3.0, p = 0.058; 76.5% vs. 23.5%, p<0.001, respectively) and day 14 (7.0+/-2.3 vs. 5.5+/-3.2, p = 0.0013; 77.8% vs. 22.2%, p<0.001, respectively). There was no association between procedure preference and sedation use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p = 0.106; day 14: OR 0.24, 95%CI 0.02-2.56, p = 0.238). 4 patients (8.5%) experienced minor self-limiting epistaxis. No serious adverse events occurred.

CONCLUSION: EG Scan was accurate for the diagnosis of any varices and clinically significant OV. Interobserver agreement was modest. More importantly, patients’ experience and preference remained significantly higher for EG Scan 14 days after procedures independent of sedation use.

Disclosure of Interest: S. Sami Financial support for research from: Intromedic Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared, R. Mansilla-Vivar: None declared, J. Fernández-Sordo': None declared, J. White: None declared, A. Khanna: None declared, M. Coletta: None declared, S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial support for research from: Intromedic Ltd, Seoul, South Korea and Olympus Keymed UK., I. N. Guha: None declared

P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE

S.H. Shin1,*, B.K. Kim1

1Department of Internal Medicine, Institue of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea, Republic Of

Contact E-mail Address:[email protected]

INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs and (2) small EVs with red sign or decompensated cirrhosis) are currently recommended for all cirrhotic patients. Recently, two new liver stiffness measurement (LSM)-based statistical equation models (PH risk score and Varices risk score) were introduced as a noninvasive, simple, accurate models for identifying presence of EVs and clinically significant portal hypertension [1].

AIMS & METHODS: We aimed to validate predictive value of the two models for detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.

Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis patients. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. LSM was measured by transient elastography; endoscopy was used as the standard for detection of EVs. PH risk score, Varices risk score and LSPS were calculated in all cases as follows: PH risk score = -5.953 + 0.188 x LSM + 1.583 x sex (1: male; 0: female) + 26.705 x spleen diameter/platelet count ratio, Varices risk score = -4.364 + 0.538 x spleen diameter – 0.049 x platelet count – 0.044 x LSM + 0.001 x (LSM x platelet count).

RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172 (25.5%) had HEVs. The area under the receiver-operating characteristic curve (AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950 (95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other factors: Varices risk score (0.907, 95% CI 0.876-0.939, p<0.001), LSM alone (0.873, 95% CI 0.842-0.904, p<0.001). At PH risk score < 4.0, 94.6% negative predictive value (NPV) was provided (481 patients), whereas 94.3% positive predictive value (PPV) was achieved (70 patients) at PH risk score > 10.0. In the same way, at Varices risk score < -2.5, 95.6% NPV was provided (413 patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score > 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients (81.6%) and 485 patients (71.9%), respectively.

CONCLUSION: The PH risk score is a reliable, noninvasive predictive model for detection of HEVs. Furthermore, the LSPS is considered as more simply applicable model having similar predictive value. Patients with PH risk score < 4.0 may avoid endoscopy safely, whereas those with > 10.0 should be considered for appropriate prophylactic treatments.

REFERENCES

1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144: 102-111.e101.

2. Kim BK, Han KH, Park JY, et al. A liver stiffness measurement-based, noninvasive prediction model for high-risk esophageal varices in B-viral liver cirrhosis. Am J Gastroenterol 2010; 105(6): 1382-1390.

Disclosure of Interest: None declared

P0044 PLALA SCORE PREDICT CIRRHOSIS PATIENT IN NONALCOHOLIC FATTY LIVER DISEASE

T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on behalf of JSG-NAFLD

1gastroenterology and hepatology, Yokohama city university, yokohama, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic and progressive liver injury in many countries1). NAFLD includes a wide spectrum of liver diseases that range from simple steatosis, which is generally a nonprogressive condition, to nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma (HCC), despite the absence of significant alcohol consumption. If NAFLD patients have liver cirrhosis, they need to be kept under surveillance for early detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in patients with NAFLD2). However, ad the number of NAFLD patients has reached 80–100 million in the United States and about 10 million NAFLD patients are estimated in Japan, it is virtually impossible to enforce in all patients.

AIMS & METHODS: To develop a mass screening system for general physicians, which can be used for predicting liver cirrhosis in NAFLD patients, using routine laboratory parameters.

A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD.

RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were selected as independent variables associated with cirrhosis in NAFLD patients by multiple logistic regression analysis. The optimal cutoff value of platelet count, serum albumin, and AST/ALT ratio was set at <15.3 104/μl (sensitivity; 81.6% specificity; 88.6%), <4.0 g/dl (sensitivity; 84.2% specificity; 84.6%), and >0.9 (sensitivity; 78.9%, specificity; 82.0%), respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AST/ALT ratio = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA ≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sensitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive predictive value).

CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

REFERENCES

1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.

2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362.

Disclosure of Interest: None declared

P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE RETROSPECTIVE STUDY

U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1

1Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre, Denmark

Contact E-mail Address:[email protected]

INTRODUCTION: Carvedilol may have a greater effect on portal and systemic hypertension than propranolol although reports are conflicting 1, 2. The impact of carvedilol versus non-specific betablockers (NSBB) on mortality on patients with cirrhosis remains to be evaluated.

AIMS & METHODS: We wanted to compare the impact on mortality of carvedilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic cirrhosis from the Danish National Patient Register during the period 1995 through 2010. We used the anatomical therapeutic chemical (ATC) classification to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk time as the time from the first prescription of either carvedilol or NSBB until death or end of follow-up (December 31, 2010). We adjusted for gender, age, heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of diuretics. We used univariate and multivariate Cox proportional hazard models to assess the HR. Persons with missing data were excluded from the analyses (0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC, USA).

RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol and NSBB, respectively. Three patients had received both carvedilol and NSBB and were excluded. Patients from the carvedilol group were mainly classified with uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we only included patients with uncomplicated cirrhosis in our mortality analysis (80 versus 1.857 patients). Significantly fewer patients in the carvedilol group died during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square p<0.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45 (95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7). The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs. 14%) prior to cohort entry were un-evenly distributed between users of carvedilol and NSBB. We did a sub-analysis where we matched patients on the presence of heart disease and variceal prior to cohort entry. In this sub-analysis we compared 80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found an adjusted HR of 0.38 (95% CI 0.2-0.7).

CONCLUSION: The use of carvedilol compared with NSBB in patients with cirrhosis was associated with lower mortality in this retrospective study.

REFERENCES

1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study. Dig Liver Dis 2014; 46: 251-256.

2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 2002; 36: 1367-1373.

Disclosure of Interest: None declared

P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD COMPONENT USE IN CIRRHOSIS

V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2, A. Burroughs3

1Nuffield Department of Medicine, University of Oxford, 2NHS Blood and Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom

INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both for prophylaxis and for treatment of bleeding, although indications and patterns of blood use are poorly characterised.

AIMS & METHODS: All NHS trusts with representation on the British Society of Gastroenterology membership list were invited to take part in a national audit. Data were collected prospectively on consecutive admissions with a confirmed diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/death/day 28. Specific information was requested on use of blood components, including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate.

RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years, 65% male) were collected from 85 hospitals. The predominant aetiology was alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all admissions were transfused a blood component; in 61% (238/391) this was for treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238) received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238) cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold was >8g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis the majority (61%, 94/153) received transfusion in the absence of a planned procedure. In patients transfused for prophylaxis prior to a procedure (59/153): 19% (3/16) received FFP at an INR ≤1.5 for high risk procedures and 33% (6/18) received FFP at an INR≤2 for low risk procedures; 36% (9/25) received platelet transfusion at a platelet count>50 prior to a procedure. The most frequent procedures resulting in prophylactic transfusion were paracentesis (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the most frequent cause of death.

CONCLUSION: Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component use is required, particularly in the group transfused for prophylaxis of bleeding. Further work is needed to improve patterns of blood use in cirrhosis to ensure patients are not exposed to unnecessary transfusion and its attendant harms.

Disclosure of Interest: None declared

P0047 SVR12 OF 99% ACHIEVED WITH A RIBAVIRIN-FREE REGIMEN OF ABT-450/R/OMBITASVIR AND DASABUVIR IN HCV GENOTYPE 1B-INFECTED PATIENTS

A. Maieron1,*, M. Puoti2, J. V. Enejosa3, P. Andreone4, Z. Ben Ari5, G. Norkrans6, M. Romero-Gomez7, W. Xie3, D.E. Cohen3, T. Podsadecki3

1Elisabeth Hospital, Linz, Austria, 2A. O. Ospedale Niguarda Ca Granda, Milan, Italy, 3AbbVie Inc., North Chicago, United States, 4University of Bologna, Bologna, Italy, 5The Chaim Sheba Medical Center, Tel Hashomer, Israel, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Hospital Universitario Nuestra Senora De Valme, Seville, Spain

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor (identified by AbbVie and Enanta) dosed with ritonavir (r). Ombitasvir (formerly ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is a non-nucleoside NS5B RNA polymerase inhibitor. We report the sustained virologic response 12 weeks post-treatment (SVR12) achieved in HCV genotype 1b-infected patients after treatment with these 3 direct-acting antivirals (3D regimen) with or without ribavirin (RBV).

AIMS & METHODS: Five hundred ninety-nine treatment-naïve and prior pegIFN/RBV-experienced HCV genotype 1b-infected patients without cirrhosis were enrolled and received study drugs in the PEARL-II and PEARL-III randomized phase 3 studies. Patients were randomized 1:1 to co-formulated ABT-450/r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice daily) with or without weight-based RBV (1000 – 1200 mg daily).

RESULTS: The combined SVR12 rate from PEARL-II and PEARL-III was 99.3% in 301 patients who received 3D regimen without RBV vs. 98.7% in 298 patients who received 3D + RBV. Two patients (0.7%) receiving 3D without RBV did not achieve SVR12, both due to missing week 12 post-treatment follow-up. Four 3D + RBV patients did not achieve SVR12: 1 (0.3%) due to virologic breakthrough, 1 (0.3%) due to missing SVR12 data, and 2 (0.7%) due to study drug discontinuation for adverse events. SVR12 rates did not differ between 3D and 3D + RBV by baseline factors including IL28B genotype, sex, age, race, ethnicity, BMI, fibrosis stage, and HCV RNA viral load. No patients receiving 3D and 0.7% of patients receiving 3D + RBV discontinued due to adverse events.

SVR12 by baseline factors, n/N (%)3D3D + RBV
Overall299/301 (99.3)294/298 (98.7)
Treatment-naïve208/210 (99.0)209/210 (99.5)
PegIFN/RBV Treatment-experienced91/91 (100)85/88 (96.6)
IL28B non-CC genotype249/250 (99.6)240/244 (98.4)
Female160/160 (100)147/149 (98.7)
Age ≥6534/34 (100)29/29 (100)
Black race16/16 (100)13/13 (100)
BMI ≥ 30 kg/m262/64 (96.9)44/45 (97.8)
Fibrosis stage, F331/33 (93.9)33/34 (97.1)

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CONCLUSION: Irrespective of previous pegIFN/RBV treatment response and other baseline factors, HCV genotype 1b-infected patients achieved high SVR rates after 12 weeks of 3D without RBV. Overall, only 1 (3D + RBV) of 599 (0.2%) patients experienced virologic breakthrough and none experienced relapse. Both regimens were well tolerated. ABT-450/r/ombitasvir and dasabuvir without RBV achieves optimal treatment efficacy in HCV genotype 1b-infected patients without cirrhosis.

Disclosure of Interest: A. Maieron Financial support for research from: Roche, MSD, Consultancy for: MSD, Janssen Therapeutics, AbbVie, Boehringer Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, M. Puoti: None declared, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, P. Andreone Financial support for research from: Roche, Merck, Gilead, Consultancy for: Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead, MSD, BMS, Z. Ben Ari Consultancy for: MSD, Janssen, AbbVie, Boehringer Ingelheim, BMS, GSK, G. Norkrans: None declared, M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, W. Xie Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: AbbVie

P0048 ADHERENCE TO PRESCRIBED DOSES OF ABT-450/R/OMBITASVIR, DASABUVIR, AND RIBAVIRIN IN THE PHASE 3 PEARL-II, PEARL-III, AND PEARL-IV TRIALS

D. Bernstein1, R. Marinho2,*, D. Cohen3, F. Bredeek4, F. Schneider5, G. Norkrans6, M. Curescu7, M. Bennett8, M. Maevskaya9, J. Fessel10, W. Xie3, Y. Luo3, J. Enejosa3

1Hofstra North Shore- LIJ School of Medicine, Manhasset, United States, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisbon, Portugal, 3AbbVie Inc., North Chicago, 4Metropolis Medical Group, San Francisco, United States, 5Markusovszky Hospital, Szombathely, Hungary, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Life Search SRL, Timisoara, Romania, 8Medical Associates Research Group, San Diego, United States, 9First Moscow State Medical Universita n.a. I. M. Sechenov, Moscow, Russian Federation, 10Kaiser Permanente, San Francisco, United States

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, dosed with ritonavir(r); ombitasvir(ABT-267) is an NS5A inhibitor; dasabuvir(ABT-333) is an NS5B RNA polymerase inhibitor. The phase 3 PEARL trials examined the efficacy and safety of all-oral, interferon-free, 12-week regimens of ABT-450/r/ombitasvir+dasabuvir(3D) with or without ribavirin(RBV) in HCV genotype(GT) 1a- and 1b-infected patients(pts). We report pt adherence to the regimens in these trials.

AIMS & METHODS: Pts were randomized to co-formulated ABT-450/r/ombitasvir(150mg/100mg/25mg QD)+dasabuvir(250mg BID) with either weight-based RBV or placebo (PBO)/no RBV. Adherence was calculated by pill counts as the percentage of capsules/tablets taken relative to the total capsules/tablets expected to be taken.

RESULTS: In each trial, mean pt adherence to every study drug was >98.5%(Table). Adherence was comparable in those who received 3D with RBV, 3D with PBO, or 3D alone. SVR12 rates were 96.6-100% in treatment-experienced and treatment-naïve HCV GT1b-infected pts receiving 3D+/-RBV. SVR12 rates were 97.0% and 90.2%, respectively, in treatment-naïve GT1a-infected pts receiving 3D+RBV or 3D+PBO. Only 1 GT1b-infected pt had virologic failure. Pts with virologic failure had adherence rates comparable to the overall rates, but the majority was GT1a-infected and did not receive RBV. Five pts had adherence rates<80% for one or more study drugs, none of whom had virologic failure. Among 401 pts receiving 3D with RBV and 509 pts receiving 3D without RBV, 2(0.5%) and 2(0.4%), respectively, discontinued study drug due to adverse events.

PEARL-II Treatment-experienced* GT1b
PEARL-III Treatment-naïve GT1b
PEARL-IV Treatment-naïve GT1a
3D+RBV3D3D+RBV3D+PBO3D+RBV3D+PBO
Adherence, Mean % (SD)
ABT-450/r/ ombitasvir99.7 (2.3) n = 87100.0 (2.6) n = 9299.8 (1.2) n = 205100.0 (1.1) n = 20599.7 (1.9) n = 9899.7 (3.3) n = 190
dasabuvir99.0(3.2) n = 9099.2 (1.6) n = 9499.8 (1.2) n = 20599.9 (1.1) n = 20599.2 (2.0) n = 9899.1 (3.6) n = 190
RBV99.1 (6.5) n = 87NA99.6 (2.1) n = 20599.6 (2.6) n = 20398.6 (3.2) n = 9098.7 (3.6) n = 181
SVR12, % (n/N)96.6 (85/88)100 (91/91)99.5 (209/210)99.0 (207/209)97.0 (97/100)90.2 (185/205)

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Adherence data for each capsule/tablet not available for all pts.

In PEARL-II, 7 randomized patients were excluded from the intent-to-treat efficacy population because they received non-coformulated ABT-450/r/ombitasvir (N = 6) or could not be genotyped (N = 1).

CONCLUSION: Participants in these phase 3 trials had excellent adherence (>98.5%) to doses of ABT-450/r/ombitasvir, dasabuvir, and RBV. Low adherence rates, while infrequent, were not associated with virologic failure.

Disclosure of Interest: D. Bernstein Financial support for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, R. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, D. Cohen Shareholder of: AbbVie, Other: AbbVie, F. Bredeek Financial support for research from: AbbVie, BMS, Gilead, Janssen, Merck, Sumagen, ViiV, Lecture fee(s) from: Merck, ViiV, Consultancy for: Merck, ViiV, F. Schneider: None declared, G. Norkrans: None declared, M. Curescu: None declared, M. Bennett Shareholder of: AbbVie, M. Maevskaya: None declared, J. Fessel: None declared, W. Xie Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie

P0049 ASSOCIATION BETWEEN TLR-3 GENE POLYMORPHISM RS3775291 AND PROGRESSION OF HEPATITIS C VIRUS INFECTION

F.-Z. Fakhir1,2,*, M. LKHIDER1

1Faculté des Sciences, Chouaib Doukkali University, El Jadida, 2Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatitis C virus (HCV) is a major global health problem with about 210 million people infected worldwide, and constitutes the most important cause of chronic liver disease. HCV is an enveloped positive-strand RNA virus belonging to the genus Hepacivirus of the family Flaviviridae. During the viral replication cycle, double-stranded RNA (dsRNA), produced as an intermediate, is sensed by several pattern recognition receptors (PRRs) of the innate immune system including Toll-like receptors (TLR). TLRs constitute a family of receptors playing a key role in innate and adaptive immune response, among them TLR3,-7 and -8, which are expressed on endosomal membrane, and have been suggested to play an important role in antiviral immune responses based on their recognition of dsRNA and single-stranded RNA (ssRNA). Single nucleotide polymorphisms (SNPs) may shift balance between pro- and anti-inflammatory cytokines, contributing to successful resistance to infection or leading to chronic inflammation and cancer. The aim of this study was to investigate the association between the TLR-3, -7 and -8 polymorphism and the outcome of HCV infection.

AIMS & METHODS: 517 patients were enrolled in the study and genotyped for the TLR3, -7 and -8 SNPs. Logistic regression was used to assess the association between the polymorphisms and the outcome of the infection.

RESULTS: A significant association between TLR-3 SNP at rs3775291 and risk of advanced liver disease was identified. The rs3775291-A/A genotype was more common in subjects with advanced liver disease than subjects with mild chronic hepatitis C (OR = 3.81; 95% CI, 2.16-6.72; p = 0.000004) and this difference was higher with healthy controls (OR = 5.34; 95% CI, 2.70-10.58; p = 0.000002).

CONCLUSION: Our findings indicate that a TLR-3 SNP rs3775291 is associated with progression of HCV infection to cirrhosis and hepatocellular carcinoma.

Disclosure of Interest: None declared

P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS

M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4, F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J. V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10

1Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital Germans TríasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and Southern California Research Center, Coronado, 7University of Pennsylvania, Philadelphia, 8The Queen’s Medical Center – Liver Center, Honolulu, 9AbbVie Inc., North Chicago, United States, 10University of Milan, Milan, Italy

INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition. We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) (3D regimen) with or without RBV.

AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials (PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of RBV to the safety and efficacy of the 3D regimen, were used to evaluate the incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia, jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were assessed at baseline and every 1-2 weeks per protocol.

RESULTS: Total bilirubin elevations of >3X ULN occurred in 23/401 (5.7%) 3D+RBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regimen. The majority of patients in each group (>90%) had normal total bilirubin levels at the end of treatment. Mean total bilirubin levels were significantly higher at each treatment visit in the RBV-containing treatment groups. Mean total bilirubin peaked at week 1 in both treatment groups (predominantly indirect), and declined to baseline by week 2 in the RBV-free group. Events of hyperbilirubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of treatment and did not result in study drug discontinuation. One patient underwent RBV dose modification and one interrupted study drug due to hyperbilirubinaemia; both patients achieved sustained virologic response 12 weeks post-treatment. Two patients receiving 3D+RBV experienced ALT ≥3X ULN and total bilirubin ≥2X ULN, however, the timing and predominance of indirect bilirubin were not consistent with drug induced liver injury. No serious adverse events related to hyperbilirubinaemia were reported.

Bilirubin-related events, n (%)3D+RBV (N = 401)3D (N = 509)
Any bilirubin-related event21 (5.2)4 (0.8)
Hyperbilirubinaemia13 (3.2)3 (0.6)
Jaundice11 (2.7)1 (0.2)
Total bilirubin >3X ULN23 (5.7)2 (0.4)

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CONCLUSION: Low rates of hyperbilirubinaemia were observed with both 3D regiments but was less frequent in the RBV-free 3D regimens, suggesting that increases in bilirubin associated with ABT-450-containing regimens are enhanced by RBV-induced haemolysis. Bilrubin-related adverse events were infrequent with both regimens and did not affect treatment response.

Disclosure of Interest: M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, R. T. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, R. Planas Vila Financial support for research from: Roche, MSD, BMS, Gilead, Janssen, Lecture fee(s) from: Roche, MSD, BMS, Gilead, Janssen, Boehringer Ingelheim, Consultancy for: Roche, MSD, BMS, Gilead, Janssen, D. Bernstein Financial support for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, F. Rodriguez-Perez Lecture fee(s) from: BMS, Merck, Consultancy for: AbbVie, Gilead, Janssen, Merck, T. Hassanein Financial support for research from: AbbVie, Boehringer-Ingelheim, BMS, Eisai, Gilead, Janssen, Idenix, Ikaria, Mochida, Takeda, Mochida, Roche, Ocera, Sundise, Salix, Taigen, Takeda, Vertex, Lecture fee(s) from: BMS, Genentech, Gilead, Salix, Consultancy for: AbbVie, BMS, K. R. Reddy Financial support for research from: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Genfit, Consultancy for: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Idenix, N. Tsai Financial support for research from: AbbVie, Janssen, Genentech-Roche, Vertex, BMS, Lecture fee(s) from: Gilead, Genentech-Roche, BMS, Vertex, Merck, Janssen, Consultancy for: AbbVie, Gilead, Janssen, S. Lovell Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, M. Colombo Financial support for research from: Merck, Roche, BMS, Gilead, Lecture fee(s) from: Tibotec, Roche, Novartis, Bayer, BMS, Gilead Sciences, Vertex, Consultancy for: AbbVie, Merck, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, Abbott, Boehringer Ingelheim, GSK, GenSpera

P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS INDEPENDENT OF PATIENT SUBGROUPS

M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5, E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7

1Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital, Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel, Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San Diego Digestive Diseases, San Diego, 6Texas Liver Institute, University of Texas Health Science Center, San Antonio, 7AbbVie, North Chicago, United States

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta; ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a non-nucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral (3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected patients, 96.3% of treatment-naïve patients (SAPPHIRE-I trial) and 96.2% of pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV RNA <25 IU/mL at post-treatment week 12).

AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were randomized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir (150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV (1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the two trials were pooled, and SVR12 rates were calculated overall and according to race, ethnicity, and region.

RESULTS:

Источник: [https://torrent-igruha.org/3551-portal.html]

REPAIR MANUAL - Euromachines

REPAIRMANUAL

NEW HOLLAND

VL570 VM370

VL610 VM460

VL620

VL630

VL640

VL660


SPECIFICATIONS

Chapter 1

CONTENT

Section Description Page

identification 3

.

Machine

4

.

Dimensions

machine technical specifications 6

.

Self--propelled

equipment technical specifications 9

.

Harvesting

604 82 321 00 -02 - 2005


2 SPECIFICATIONS

604 82 321 00 -02- 2005


SPECIFICATIONS 3

MACHINE IDENTIFICATION DATA

Model Type Serial number Machine number

VL 660 664 001 001

VL 640 660 001 001

VL 630 660 001 001

VL 620 656 001 001

VL 610 656 001 001

VM 460 636 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

657 001 001

637 001 001

VL 570 655 001 001

VM 370 633 001 001

harvest-

VL

equipinge

ment

harvest-

VM

equipinge

ment

A = Manufacturer’s label

B = Stamped frame number

VL 610 ÷ 660 and VM 460: 604801000 (GB)

VL 570 and VM 370: 604801300 (GB)

Reference:

654 001 001

634 001 001

OPERATOR’S MANUAL

SPARE PART CATALOGUE

604 82 321 00 -02 - 2005


4 SPECIFICATIONS

604 82 321 00 -02- 2005

2100 litres

2600 litres

3200 litres


SPECIFICATIONS 5

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Code DIMENSIONS (mm)

H1 Height: without cab

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3810 3810

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 2000 to 2600

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 2600 l

HB5 Height under clearance hoppers, 3200 l

E Wheelbase 2860

La1 Max. width at the hoppers hoppers, 2100 l 2500/2300

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

2100 l + cab 3000/2800

2600 l or 3200 l 3000

self--propelled

Only

machine

self--propelled

Only

machine

2590 2390

2830 2630

LaB1 Hopper width 2100 l 2500 2300

2600 l

LaB2

l 3200

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 + Gb = La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 28

420/85

Tyres

R 28

480/70

Tyres

R 28

540/65

to front wheels Tyres

next

R 24

420/70

3000

3000

2800

2160 + 454 = 2614 1790 + 454 = 2244

2260 + 480 = 2740 1860 + 480 = 2340

2340 + 540 = 2880

Tyres 600x55x30.5 2360 + 600 = 2960

1930 + 420 = 2350 1730 + 420 = 2150

(V2 + Gb = La AV) Tyres 13.6 R 24 1930 + 350 = 2280 1730 + 350 = 2150

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

without cab 5390

with cab 5500 (5650)

DAV1 Front offset: without cab 910

DAV2 with cab 1050

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

604 82 321 00 -02 - 2005


6 SPECIFICATIONS

604 82 321 00 -02- 2005

1800 litres

2400 litres or 2200 litres


SPECIFICATIONS 7

COMMERCIAL DESCRIPTION VL 570 VM 370

Code DIMENSIONS (mm)

H1 Height: without cab 3160 3040

(in road position) with cab (at the

H2

beacon)

revolving

Harvesting equipment

H3

height

3600 3420

to the railings 3680 3530

H4 Clearance under the harvesting equipment from 1800 to 2300 from 1950 to 2450

HB1 Clearance under tilted up hoppers

HB2 Tilting axle height

HB3 Max. height with lifted hoppers

HB4 Height under clearance hoppers, 1800 l

HB5 Height under clearance hoppers, 2400 l

E Wheelbase 2730

La1 Max. width at the hoppers hoppers, 2400 l

Max. width from cover to

La2

cover

Max. width from cab top to

La3

cover g right

l + cab

2400 l +cab

2400

self--propelled

Only

machine

self--propelled

Only

machine

2540 2340

2750 2540

LaB1 Hopper width 1800 l 2500 2300

2200 l

LaB2

l 2800

2400

AR Outer width

La

to rear wheels:

next

Gb L AR)

(V1 +Gb=La AR)

(V1

tracks: 2tracks: 2

track = narrow track +

large

mm 160 mm 160

track = standard,

Large

in this table

shown in this table

shown

La AV Outer width

Tyres

R 24

420/70

Tyres

R 24

480/65

Tyres

R 24

460/70

Tyres

R 24

340/85

Tyres 11.2R24

to front wheels Tyres

next

R 20

280/70

+ Gb = La AV) Tyres

(V2

R 20

320/70

(V2 at ground level)

Max. length

Lo1

(with) destemmers

without (with) destemmers

without

Lo2

DAV1 Front offset: without cab

DAV2 with cab

DAV3 Offset of front supports for multipurpose

DAR Rear offset

Note: in road position, the noria is at 200 mm from the ground

2065 + 431 = 2496

2095 + 484 = 2579

2095 + 462 = 2557

2800

1975 + 366 = 2341 1775 + 366 = 2141

1755 + 291 = 2046

1694 + 275 = 1969

1942 + 315 = 2257 1742 + 315 = 2057

without cab 4910 (5110)

with cab 4980 (5180)

604 82 321 00 -02 - 2005


8 SPECIFICATIONS

WEIGHT

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

PTAC Total allowed weight under load (kg) 9500

Partition front axle (kg)

rear axle (kg)

4200

5300

weight with harvest- Total 8700 (9200)

Empty weight with harvest Total 8700 (9200)

Empty

equipment and without

g q p ing

(with) destemmers

Weight of one wheel (kg) 420/70 R 24

Thermal engine weight (kg)

FEEDING/EXHAUST

480/70 R 28

540/65 R 28

Fuel tank Used fuel

Capacity (litres)

Diesel oil

Engine feeding system Direct injection

Air filter Make

Type

Engine cooling Water capacity (litres)

250

DONALDSON

ELB 12--0265

Fan Sucking

Cooling fan ∅ (mm) 610 584

DRIVE

Pump for engine fan Make

Displacement (cm�/rev.)

Empty operating speed

(rpm)

Capacity (l/minute), output

0.9

Fan motor Make

Variable flow inching hy-

draulic pump:

Displacement (cm�/rev.)

Make

Type

Total displacement

(cm�/rev.)

SAUER

17

(1.02 x engine speed)

35

SAUER

12.2

REXROTH

A4VG

from 0 to 105


DRIVE (follows)

SPECIFICATIONS 9

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Priming pump Displacement (cm�/rev.)

Capacity (l/minute), output

0.9

Front wheel motor Make

Type

Rear wheel motor Make

Displacement (cm�/rev.)

Type

Displacement (cm�/rev.)

26

57.3

POCLAIN

MS 08

1043

POCLAIN

MSE 18

2636 (1406/1230)

Max. speed (km/h) in road position 25 km/h

Max. speed (km/h) in field position 12

Hydraulic oil

Capacity l/minute

Oil type

Extractor pump and con-

veyors

Shaking

pump

Steering/lifting/hopper pump

Total

Reservoir 65

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

Make

Displacement (cm�/rev.)

Idle operating rpm speed

Capacity (l/minute), output

0.9

NEW HOLLAND: Hydrosystem 68

Hydrosystem 68 BIO S

REXROTH

”Load sensing” from 0 to 45

2500 (see engine speed)

101.2

SAUER

22

2500 (see engine speed)

50

SAUER

14

(1.02 x engine speed)

STEERING Hydrostatic

Type EATON QAMP 146 cm�/rev.

BRAKING

Service brake Supplied by the hydrostatic transmission

Parking brake (acting on the two rear wheels) Operated by ONE pedal and by the steering

Parking brake Operated by left manual lever

29

604 82 321 00 -02 - 2005


10 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

TILTING CORRECTION 30%

PLATFORM CAB

Heated and air--conditioned cab Depending on the model

Activated charcoal filter Option

On--board computer �

Grand--Luxe seat

Pneumatic seat �

Multi--function lever �

LIGHTING AND WARNING LIGHTS

High/low beams 2

Front parking lights 2

Rear parking lights 2

Direction indicator warning lights Front

Rear

Side

Stop lights 2

License plate light 1

Reflector Rear 2

Revolving beacon with cab 2

Supply voltage / battery 12 V / 180 Ah

Alternator 120 A

2

2

2


HARVESTING EQUIPMENT

HARVESTING HEADER

SPECIFICATIONS 11

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

Type Swinging, self--aligning

System Shaking, SDC

Number of shakers 14

Straight/elbow connecting rod 13/1

Shaking drive Motor manufacturer

Displacement (cm�/rev.)

ECU:

Ratio

Toe--in adjustable from the operator’s seat

Grease: TUTELA MRM2

SAUER

Amplitude settings 4

22

4/1

2.7 kg

Min. clearance under the frame (mm) 2000

Grape harvesting useful height (mm) 1650

Harvesting tunnel width (mm) 500

604 82 321 00 -02 - 2005


12 SPECIFICATIONS

604 82 321 00 -02- 2005

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

RECEIVING/TRANSPORTATION

Noria system Buckets per chain

Type

Synchronized

63/61

XXL/small

in field speed

Width of flexible stock guides (mm) from195to265

Tightness length (mm) 2100

Harvesting min. height (mm) 150

Drive Motor manufacturer

Harvesting conveyors Width (mm)

Displacement (cm�/rev.)

Max. operating speed rpm

Reverse

Single operation Motor manufacturer

Displacement (cm�/rev.)

EATON

500

600

about 750

yes

EATON

31.6


CLEANING

SPECIFICATIONS 13

COMMERCIAL DESCRIPTION VL 610 ÷ 660 VM 460

2 upper extractors with removable

stalk choppers

2 lower extractors with

2 independent stalk choppers, en-

abled by shaking

HOPPERS

Diameter (mm)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Diameter

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Drive

Motor manufacturer

Displacement

(cm�/rev.)

Direction of rotation

460

hydraulic

SAUER

11

430

Hydraulic system

SAUER

6

Hydraulic system

EATON

8.2

reverse to the wheels

Capacity 2 x 1600

2 x 1300

2 x 1050

Electrically--operated distribution auger Control independent of the grape harvester

604 82 321 00 -02 - 2005


14 SPECIFICATIONS

604 82 321 00 -02- 2005


WEIGHT

SPECIFICATIONS 15

COMMERCIAL DESCRIPTION VL 570 VM 370

PTAC Total allowed weight under load (kg)

Partition front axle (kg)

Empty weight with

harvesting equipment

and without (with)

destemmers

Weight of one wheel

(kg)

rear axle (kg)

Total

Thermal engine weight (kg)

FEEDING/EXHAUST

Fuel tank Capacity 160 litres * *

4--cylinder engine --

-- ISO power (KW/CV)

-- Displacement = 1125 cm 3 /cylinder

Air filter Make

Type

Engine cooling Liquid capacity (litres)

Fan

94/128

Air/air intercooler * *

DRIVE

Variable displace-

ment inching hy-

draulic pump:

”Rexroth” A4VG90

Displacement elimin-

ation:

Drive:

Total displacement

90 cm�/rev.

*

*

electr.

*

94/128

*

*

electr.

*

604 82 321 00 -02 - 2005


16 SPECIFICATIONS

DRIVE (follows)

COMMERCIAL DESCRIPTION VL 570 VM 370

Priming pump Displacement 25 cm�/rev.

604 82 321 00 -02- 2005

Capacity (l/minute), output

0.9

Front wheel motor Make ”Poclain”

Type MSE 05

Displacement 688 cm�/rev.

Rear wheel motor Make ”Poclain”

Type MSE 11

Displacement 843/843

cm�/rev.

* *

Double steering valve * *

Front drive wheels in road position * *

”Twin lock” antiskid * *

Torque reduction on front wheels, optional * *

Max. speed in road position, 25 km/h * *

Max. speed in field position, 12 km/h * *

Hydraulic oil

Capacity l/minute

Oil type

Total

Reservoir, 65 PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen Holland

Hydrosystem 68

Hydraulic filtering (intake/return) * *

Extractor pump and

conveyors

Shaking

pump

Make ”Sauer”

Displacement 44 cm�/rev.

Idle operating rpm speed =

engine

Capacity (l/minute), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, output

0.9

Make ”Sauer”, double

Displacement 22 cm�/rev.

Idle operation rpm speed =

93% of engine speed

Capacity (l/minute), output

0.9

*

*

*

*

*

*

*

*

*

*

*

*


SPECIFICATIONS 17

COMMERCIAL DESCRIPTION VL 570 VM 370

Steering/lifting/hopper

pump

STEERING

Make ”Sauer”, double

Displacement 11 cm�/rev.

Idle operation rpm speed

= 93% of engine speed

Capacity (l/minute), output

0.9

Type: ”Eaton” valve, 100 cm 3 /rev. * PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen service brake * *

Parking brake (acting on the two rear wheels) * *

Manually--operated parking brake, on the left * *

Electrically--operated independent brakes No No

*

*

604 82 321 00 -02 - 2005


18 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

TILTING CORRECTION

Max. tilting (%) 25 25

Max. tilting in road position (%) 8 8

Max. tilting in work position (%)

(with destemmers or special implement and

front wheels with ballasts)

FRAME

604 82 321 00 -02- 2005

32 32

Harvesting header quick uncoupling * *

Link fitting possibility * *

Front and rear tracks = see relevant SB * *

PLATFORM CAB

Heated and air--conditioned cab

Activated charcoal filter

ELTEC control panel * *

Imitation leather seat as standard outfit * *

Pneumatic seat, with cab, optional * *

Multifunction lever, number of push buttons 18 18

Electrical inching control, adjusted through

sensors (optional radar)

Electrical presetting for:

-- electrically--operated rear view mirrors

-- CDHA

-- rear viewing

* *

*

*

*

*

*

*


SPECIFICATIONS 19

COMMERCIAL DESCRIPTION VL 570 VM 370

LIGHTING AND WARNING LIGHTS

High/low beams

Front parking lights

Rear parking lights

Direction indicator

warning lights

Stop lights

License plate light

Front

Rear

Side

Reflector Rear

Revolving beacons

Battery, capacity (AH) 135 135

Alternator -- 120 A * *

604 82 321 00 -02 - 2005


20 SPECIFICATIONS

COMMERCIAL DESCRIPTION VL 570 VM 370

HARVESTING EQUIPMENT

HARVESTING HEADER

Harvesting header hour counter yes yes

Type -- swinging, self--aligning * *

SDC shaking system * *

Number of shakers 14 12

Straight/elbow flexible connecting rod 13/1 11/1

Shaking drive ”Sauer/Eaton” motor

Toe--in adjustable

from the operator’s

seat

604 82 321 00 -02- 2005

Displacement

(cm�/rev.)

Reducer control unit:

1/4

Grease: GR75MD

22

*

22

* *

Amplitude settings 3 3

Removable shakers, optional * *

Min. clearance under the frame

1950/2450 mm

Min. clearance under the frame

1800/2300 mm

Grape harvesting useful height (mm) 1050 900

Harvesting tunnel

width (mm)

RECEIVING/TRANSPORTATION

Noria system Large buckets

Small buckets

Fastening by 2 plates

Drive gears:

16/59

17/58

Width of flexible stock guides (mm) 195/265 165/235

Tightness length 1750 mm * *

Min. harvesting height 150 mm * *

Operation ”Eaton” motor

Displacement 395

cm�/rev.

*

55

*

*

*

*

53

* *

*


SPECIFICATIONS 21

COMMERCIAL DESCRIPTION VL 570 VM 370

Harvesting con-

veyors

Width 450 mm

Max. operating speed

rpm

Reverse

Single operation ”Eaton” motor

CLEANING

2 upper extractors

with removable

stalk choppers

2 lower extractors

(optional)

2 independent stalk

choppers, enabled

by noria in propor-

tional

HOPPERS

Capacity

Displacement 31.6

cm�/rev.

Diameter 430 mm

”Sauer” motor

Displacement 11

cm�/rev.

Electrically--operated

speed

Diameter 430 mm

”Sauer” motor

Displacement

6cm�/rev.

Electrically--operated

speed

”Eaton” motor

Displacement

8.2 cm�/rev.

*

*

* *

1800 litres *

2360 litres *

Distribution auger

”Eaton” motor

Displacement

31.6 cm�/rev.

Adjustable speed

*

*

*

*

*

*

*

* *

*

*

*

*

*

604 82 321 00 -02 - 2005


22 SPECIFICATIONS

604 82 321 00 -02- 2005


Section Description

00 Maintenance

REPAIRMANUAL

CONTENT

05 Machine preparation and equipment

10 Engine

14 Live PTO

29 Hydrostatic transmission

33 Brakes & Controls

35 Hydraulic systems

36 Pneumatic systems

37 Sketch 63.1 Crack Mac Archives hooks and ballasting

39 Frames

41 Steering

44 Wheels

50 Cab climate control

55 Electrical systems

58 Attachments/headers

60 Product feeding

74 Cleaning

80 Grape storage -- hoppers

88 Accessories

90 Platform, cab, bodywork and decals

1

604 82 321 00 -02 - 2005


2

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 1

SECTION 00 - MAINTENANCE

Chapter 1

CONTENT

Description Page

.

Section

Capacities 2

.

00.000

engine maintenance 3

.

Thermal

5

.

Greasing

filter 8

.

Hydraulic

9

.

Washing

system maintenance 13

.

Hydraulic

maintenance and winter storage 15

.

Routine

604 82 321 00 -02 - 2005


2 SECTION 00 - MAINTENANCE - CHAPTER 1

Item to be serviced

Self--propelled machine

greasers

604 82 321 00 -02- 2005

CAPACITIES

LUBRICANTS AND FLUIDS

Quantity

dm3 (litres)

Recommended

product

Grease

AMBRA GR 9

International

classification

Lithium--calcium based grease,

consistency NLGI 2

Harvesting machine greasers Grease 24 cartridges

Noria ECU 1 Food type re. 62777339

Shaking rear connecting rod

articulations

Shaking ECU 2.7 kg GR 75 MD

Engine sump and filter/s

6--cylinder engine

4--cylinder engine

15

9.5

Grease Teflon silicone grease

NH 720 A

Oil

AMBRA SUPER GOLD

HSP

15W - 40

Reservoir 65 Oil

AMBRA

HYDROSYSTEM 68

Cooling system 20 AMBRA

AGRIFLU (50%) +

Clean water (50%)

Sitef degree 3

410--g cartridge, re. 920019780

Re.: 661874

molybdenum bisulfide grease,

consistency NLGI 2

SAE 15W40

API CH -- 4

ACEA E3/E5

ISO 68

DIN 51524 -- part 2


a) After the first 50 hours

SECTION 00 - MAINTENANCE - CHAPTER 1 3

-- Let the engine run until it reaches the stan-

dard operating temperature.

-- Replace the diesel oil filter cartridge/s.

-- Check alternator and compressor belt ten-

sion.

-- Check engine tightness.

b) Every day or every ten hours, check:

-- the oil level,

-- the coolant level,

-- the PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen core cleanliness.

THERMAL ENGINE MAINTENANCE

c) Every 400 hours, or before each harvest-

ing season, replace:

-- the engine oil;

-- the oil filter cartridge/s;

-- the diesel oil filter cartridge/s;

-- Check belt tension.

-- Check the radiator core cleanliness.

-- If the air filter clogging indicator comes on,

clean the main cartridge windows 8.1 iso download Archives - Download Pro Crack Software compressed

air, blowing inside out.

Be careful not to use a pressure over

6 bar; shift the nozzle downwards and hold

it at about 3 cm from the paper.

d) Only before each harvesting season:

-- replace the air filter main cartridge.

NOTE: the diesel oil filter cartridges should be re-

placed more often if the diesel oil conditions require

it.

604 82 321 00 -02 - 2005


4 SECTION 00 - MAINTENANCE - CHAPTER 1

14

20

13

19

10

E

F

604 82 321 00 -02- 2005

18

11

12

16

A B

1 2 3 4 5 6 7 8

17

15

10 11 12

19 20

9

13 14 15 16 17 18

D

C

1 2 3 4 5 6 7

8 9 10 11 12 13

14 15 16 17 18 19 20

4

6

2

8

1

3

5

7

VM 460

9

VL 610 ÷ 660


SECTION 00 - MAINTENANCE - CHAPTER 1 5

GREASING POINT POSITION - VL 610 ÷ 660 and VM 460

The greasing ramp is located on the harvesting

equipment central gangway. All these points must

be greased with food--type grease every day, after

washing.

A) Noria drive shaft

B) Shaking control shaft

C) Right shaking control connecting rod

D) Left shaking control connecting rod

E) Right shaking plate

F) Left shaking plate

There is no centralized greasing on the self--pro-

pelled machine, thus you need to grease daily only

the following:

-- 2 x 3 greasers on the front legs

HARVESTING EQUIPMENT

These positions are not localised and should be

greased every 50 hours:

� 2 x 2 greasers on the hopper cylinder axes

� 2 x 1 greaser on the lower stalk choppers

TOTAL: 26

SELF -PROPELLED MACHINE

To grease every 50 hours:

� 2 x 1 greaser on the steering cylinder pivot

� 2 x 2 greasers on the steering bar pivots

� 2 greasers on steering relay

� 2 x 2 greasers on the wheel link pivot

� 2 x 2 greasers on the rear lifting cylinder

TOTAL: 16

604 82 321 00 -02 - 2005


6 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 7

GREASING POINTS FOR VL 570 and VM 370

Position and number of greasers Greasing frequency

SELF -PROPELLED MACHINE

Front legs 2 x 3 6

10 h 50 h

Steering cylinder articulation 2

Steering relays 2

Steering bar ball joints 4

Rear wheel link articulation 2 x 2 4

Rear lifting cylinder articulation 2 x 2 4

Total 22

HARVESTING EQUIPMENT

Shaking front plate 2 x 2 4

Shaking control link rods 2 x 2 4

Right side shaking shaft bearing 1 1

Left side noria shaft bearing 1 1

Belt bearings 2x4 8

Hopper tilting cylinder 2x1 2

Hopper articulation 2x1 2

Harvesting equipment rear articulation 1 1

Lower stalk chopper 2 x 1 2

Total 25

604 82 321 00 -02 - 2005


8 SECTION 00 - MAINTENANCE - CHAPTER 1

Hydraulic filter cover

During reassembly, pay attention to the assembly

direction:

-- the A side with only one arrow on the cover

must be directed towards the return line;

-- the B side with two arrows on the cover must

be directed towards intake lines.

604 82 321 00 -02- 2005

A

B


To avoid the building up of sugar and dirt in the

harvesting equipment and to preserve the grape

harvesting quality, the machine must be washed

once or several times a day, and above all at the

end of the work.

The self--propelled machine washing must take

place with standstill thermal engine; anyway, for

cleaning the harvesting equipment in the best way,

it is necessary to start the norias, the conveyors

and the extractors, after having positioned the ma-

chine in a stable place. This is anyway a depar-

ture from the general safety requirements

specified in the Operator’s Manual.

This operation calls for close attention and strict

adherence to the following rules:

SECTION 00 - MAINTENANCE - CHAPTER 1 9

� first of all, this operation must be made by a

single operator, skilled in the control of this

machine.

� The machine should be placed in a stable

cleaning area, preferably on a level con-

crete floor measuring at least 5x8 m, pro-

vided with drainage facilities and consistent

with current environmental protection re-

gulations.

The cleaning area should be equipped with the

following:

� a hose with min. diameter 35 mm, long

enough to enable the washing all around the

machine;

� a sufficient flow of water to provide a 2--m jet,

or alternatively a heavy--duty pumping unit

with3to4m 3 capacity water storage tank;

� an adjustable nozzle to direct the water jet to

about 5 m;

� a ladder, 3.5--m high and a 0.7--m long hook.

NOTE: the use of a high pressure cleaning machine

is definitely not recommended.

WASHING THE MACHINE

PREPARING THE MACHINE FOR THE

WASHING AT THE END OF THE CAM-

PAIGN

Before emptying the last hoppers, stop the thermal

engine.

-- Getoffthedriver’sseatand,frominsidethe

harvesting machine, scroll the harvested prod-

uct gathered around the shaking plates and the

rear frame into the buckets.

-- Make an inspection all the machine round and,

starting from the ground, ESET Cyber Security Pro Crack [v8.7.7] License Key 2021 Free Download any impu-

rities or deposits sticking to the surfaces.

-- Climb onto the driver’s seat, start the thermal

engine, the extractors, the conveyors and the

norias in washing position. Run the engine for

10 seconds, then empty the hoppers.

604 82 321 00 -02 - 2005


10 SECTION 00 - MAINTENANCE - CHAPTER 1

After entering the washing area, lower the machine

to 10 cm from the ground and tilt the hoppers fully.

Make sure the inching lever is in neutral, engage

the hand brake, stop the thermal engine, get off

the tractor and position the hopper safety stops.

-- Place the ladder at the rear of the machine and

climb onto the rear arch. Using the hook, pull

off any vine shoots built up or sticking to and

around the plastic safety cover.

-- Shift the ladder and lay it against the pipe

where the side plates are fastened, so as to

release the elastics holding the plates and

make the residues behind fall down.

Make sure that the plate upper part folds

correctly against the lower one, to prevent

it from being trapped in the hoppers during

tilting.

This operation must be carried out on both ma-

chine sides.

-- Remove the ladder and the hopper stops.

-- Detach the elastics from the rear sealing plates

and remove any debris trapped behind.

-- Remove any plastic plugs sealing the lower

rear part of the norias.

-- Climb onto the driver’s seat and operate the

engine at medium speed, lower the hoppers,

engage the extractors and conveyors, then

place the norias in the washing position.

-- Get off the tractor, leaving the harvesting ma-

chine working parts in operation.

604 82 321 00 -02- 2005

WASHING (in the washing area)

this is a departure from

CAUTION:

general safety requirements specified in the

the

Operator’s Manual.

-- Open the water supply valve, pick up the hose

without the nozzle and climb onto the harvest-

ing machine operating platform located behind

the driver’s seat. From here, thoroughly wash

the top of the machine, the conveyors, the

hopper augers, the norias, etc. for about 10

minutes.

-- Get off the machine and, starting from the

ground, clean the inside of the tunnel from the

front of the harvesting machine:

� plates, shaking frame, shakers;

� then, inject water into the front LH and RH

baffles through the holes provided.

-- Now go to the back of the machine, open the

saloon doors and clean the rear part of the

harvesting machine tunnel:

� the shaking frame assembly, paying special

attention to the shaker connecting rods;

� the plates and the lower sealing sheets.

-- Inject water through the side openings in the

conveyor housings.

-- Sprayalotofwaterinthehoodsofthelower

extractors, remaining at a sufficient distance

from the stalk choppers.

the extractor rotors are

DANGER:

with stalk chopper knives.

fitted

Do not try and fit the pipe or the nozzle when the

thermal engine is running.


-- Now wash the rear outer part of the machine,

SECTION 00 - MAINTENANCE - CHAPTER 1 11

carefully cleaning the inside of the rear deflec-

tors. Inject water into the rear LH and RH de-

flectors through the holes provided.

-- Lay down the hose (shutting off the water sup-

ply, if necessary) and climb onto the tractor.

Raise the RH hopper for about 50 cm, just

enough to uncover the extractor intake hood.

-- Place the left hopper in the same position.

-- Increase the engine speed to maximum.

-- Get off the tractor, retrieve the hose and climb

onto the harvesting machine platform. Wash

the inside of the extractors by flooding them

with water, one after another, at 7--second in-

tervals.

-- Get off the harvesting machine platform, shut

off the water supply, climb onto the tractor and

stop the harvesting functions (extractors, con-

veyors and norias).

Option

At this stage you can check the extractor

chutes for cleanliness by opening the in-

spection doors provided. First make

sure that the stalk choppers have come

to a complete stop.

-- Operate the machine to empty the hoppers

and return to the washing area.

-- Raise the machine to mid--height and tilt the

hoppers completely, stop the thermal engine

and engage the parking brake.

-- Getoffthetractor,fitthenozzletothewater

hose and open the water supply. One side

after the other, direct the jet toward and around

each conveyor, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, paying special attention to the

lateral opening of the conveyor housings, to

the plates, etc.

-- From the back side of the machine, wash the

hoppers and the hopper auger ends.

� Inspect the machine again and wash the

wheel links, the wheels, the safety covers,

the lower extractor outlets, the cab, etc.

� Shut off the water supply and open the con-

veyor housing inspection doors through the

inside of the harvesting machine tunnel.

-- Climb onto the tractor, start the engine and set

it to idling. Lower the machine keeping the

hoppers lifted, start the extractors, the con-

veyors, the shaking and norias in washing

position. Operate the machine for 2 to 3 min-

utes to allow the water to drain off.

After cleaning has EDIUS Pro 10.20 Crack With Serial Key 2022 Download [Latest] completed, the machine

will be ready for daily lubrication.

NOTE: after greasing, remember to reposition the

inspection doors, the plates, etc. which were

opened during the washing operations.

604 82 321 00 -02 - 2005


12 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 00 - MAINTENANCE - CHAPTER 1 13

HYDROSTATIC AND HYDRAULIC SYSTEM MAINTENANCE

1) Intake and return filter cartridge replace-

ment

This cartridge must be replaced:

a) every 800 hours,

b) or every two years,

c) at each discharging.

2) Draining and refilling the circuit

Drain the circuit every 800 hours and at least every

two campaigns.

Always observe the following recommendations:

a) fill the oil reservoir completely with the recom-

mended oil immediately at the end of the cam-

paign, to prevent condensate from forming be-

tween two seasons.

The oil must be filled by means of a pump

through the quick return coupling, so as to filter

the oil, or through the suitable fitting.

b) Before the following campaign and, compulsor-

ily, before starting the thermal engine, empty

the tank partially to ensure a perfect oil settling.

c) Check the oil level in the reservoir.

IMPORTANT: when topping oil up, use the same

type used for the initial filling.

When draining oil, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, work with great care and cleanli-

ness. Clean by a jet of compressed air or a clean

brush and oil the drain and filling holes before disas-

sembling them, so that no foreign impurities or

matters enter the circuit.

Remove the drain nut under the reservoir. Empty the

reservoir only.

During drain operations, replace the cartridges of the

intake filter and of the return filter.

604 82 321 00 -02 - 2005


14 SECTION 00 - MAINTENANCE - CHAPTER 1

604 82 321 00 -02- 2005


ROUTINE MAINTENANCE

Engine

SECTION 00 - MAINTENANCE - CHAPTER 1 15

-- Oil change every 400 hours or once a year

(incaseofACEAE3orE5oil).

-- Oil and fuel filter change every 400 hours

or once a year.

-- Belt tension adjustment every 400 hours or

onceayear.

-- Level check and cleaning of the radiator

core every day, or every 10 hours.

-- Tappet adjustment every 1200 hours (see

section 10).

-- Injector calibration adjustment every 1200

hours (see section 10).

IMMEDIATELY AFTER EACH CAMPAIGN

Disassemble:

-- the shakers without the link rods

-- the right and left bucket chains

-- the conveyor belts.

Carefully clean the above assemblies.

Repair broken buckets and removed small blocks.

in a ventilated room, protected against ro-

Store

dents:

the bucket chains, which PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen be ex-

--

to prevent bucket deformation.

tended

the conveyor belts, which should be laid

--

transversely.

out

-- the shakers, which should be laid out flat.

Carefully clean the rail assembly and the conveyor

bodies, using a water jet. Drain the inside water.

Check that no harvest residue remains in the ma-

chine.

WINTER STORAGE

Hydraulic system

-- Oil change every 800 hours or every 2

years.

-- Oil filter change every 800 hours or every

two years.

-- Protection sleeve condition control.

-- Detection and repair of possible leaks.

-- Priming and exchange pressure control.

Mechanical system

Wheel tightening check (see section 44)

every 50 hours and then every 400 hours.

Steering limiter adjustment check (see sec-

tion 41) every 50 hours and then every 1200

hours.

AFTER WASHING

for wear on the inner side of the rails and

Check

slides.

the machine assembly (self--propelled ma-

Grease

+ harvesting machine).

chine

the harvesting devices (shaking, con-

Operate

etc.) for half an hour.

veyor,

all the grease fittings on the harvesting ma-

Refill

(shaker link rods, shaking system controls,

chine

front plate and bottom roller greasers).

Replace the worn or damaged parts.

the machine (or just the harvesting machine)

Store

a covered, closed and dry area.

in

the machine on blocks to relieve the tyres,

Support

whichshouldbeleftinflated.

up the paintwork as necessary and replace

Touch

defaced safety decals.

any

the operation of the steering valve (push

Check

return).

button

Retract all cylinders and grease all unpainted

mechanical parts (shafts, pins, adjustment rods,

cylinder rod outlet ends, rails, slides, antiskid valve

push button, etc.).

604 82 321 00 -02 - 2005


16 SECTION 00 - MAINTENANCE - CHAPTER 1

Self -propelled PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen not used as multi -

function

Completely fill the fuel tank and the hydraulic res-

ervoir to prevent condensation.

Make sure the concentration of antifreeze in the

cooler is sufficient for local temperature conditions.

Change the thermal engine oil and the oil filters.

Bleed the fuel filters.

Seal the intake and exhaust ports, making them

tight.

Detach the battery, clean and recharge it, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Grease

the terminals with acid--proof grease.

604 82 321 00 -02- 2005

ONCE A MONTH:

-- remove a small amount of oil from the hydraulic

reservoir.

-- Remove the intake and exhaust port guards.

-- Assemble the battery again.

-- Operate the engine on road and let it run for the

time required to reach a temperature by about °.

-- Operate all the machine parts (extractors, con-

veyors, lifting, steering. .).

-- PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen the cab air conditioning system.

-- Stop the engine.

-- Top up the hydraulic reservoir.

-- Remove the battery.

-- Refit the intake and exhaust port guards.


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 1

SECTION 05 - MACHINE PREPARATION AND EQUIPMENT

Chapter PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen Page

.

Section

adjustment 2

.

Console

604 82 321 00 -02 - 2005


2 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005

22 mm

B

7�

A

45 mm


SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1 3

INCHING CONSOLE

1) This console can be adjusted forwards and backwards by 45 mm. To this purpose, loosen the two lock--

nuts (A) and the screw PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen inside the housing.

2) The inching lever can be adjusted as for its height -- 22 mm -- and its sloping is adjustable by 7�; tothis

purpose, loosen the three screws (B).

CHECKS

Check all levels:

-- engine oil

-- hydraulic oil

-- coolant

-- windscreen washer fluid

Check all the machine functions.

SHAKER ASSEMBLY

After analyzing the vineyard structure, assemble the shakers following the instructions of section 58.

604 82 321 00 -02 - 2005


4 SECTION 05 - MACHINE PREPARATION AND EQUIPMENT - CHAPTER 1

604 82 321 00 -02- 2005


SECTION 10 - ENGINE - CHAPTER 1 1

SECTION 10 - ENGINE

Chapter 1 - Engine

CONTENT

Operation Description Page

specifications 2

.

General

5

.

Data

torques 15

.

Tightening

17

.

Tools

views 18

.

Engine

diagram 20

.

Lubrication

diagram 22

.

Cooling

diagnosis 26

.

Fault

001 30 Engine. Compression Test 30

.

10

001 53 Engine D.A. Checks, measurements and repairs 31

.

10

102 70 Crankshaft front seal -- Replacement 94

.

10

102 74 Crankshaft rear seal -- Replacement 96

.

10

106 12 Valve tappet and rocker arm clearance -- Adjustment 100

.

10

218 30 Engine injector R.I. 101

.

10

246 14 Bosch injection pump R.I. Timing. Air bleed 102

.

10

402 10 Coolant pump R.I. 110

.

10

402 30 Thermostat valve R.I. 112

.

10

414 10 Coolant pump and generator drive belt. Tension adjustment 113

.

10

604.82.321.00 -02 - 2005


2 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen 6 cylinders

Engine, technical type:

model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601

--

pump)

(BOSCH

604.82.321.00 -02- 2005

Seedataonpage6

-- model VL610 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL620 -- type F4GE0684G*D600 (BOSCH pump) Seedataonpage7

-- model VL630 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL640 -- type F4GE0684E*D600 (BOSCH pump) Seedataonpage8

-- model VL660 -- type F4GE0684C*D600 (BOSCH pump) Seedataonpage9

Cycle . diesel, 4--stroke

Fuelinjection .

Direct

Numberofcylindersinline. 4 6

Piston diameter

mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620 -- VL630

--

. 4.094 in. (104 mm)

--VL640--VL660

Pistonstroke . 5.197 in. (132 mm)

Total displacement:

-- modelVM460--VM370--VL570 . 4485 cm 3

-- mod.VL610--VL620--VL630--VL640--VL660 . 6728 cm 3

ratio for Mod. VM460 -- VM370 -- VL570 --

Compression

VL620--VL630--VL640--VL660 . 17,5:1

VL610--

Maximum power:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 94 kW (128 HP)

-- modelVL610--typeF4GE0684G*D600 . 107 kW (145 HP)

-- modelVL620--typeF4GE0684G*D600 . 107 kW (145 HP)

-- modelVL630--typeF4GE0684E*D600 . 120 kW (160 HP)

-- modelVL640--typeF4GE0684E*D600 . 120 kW (160 HP)

-- modelVL660--typeF4GE0684C*D600 . 129 kW (175 HP)

Maximumpowerspeed . 2300 rpm

Maximum torque: model VM460 -- VM370 -- VL570 -- type

--

F4GE0484C*D601

500 (Nm)

-- Maximum torque: model VL610 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL620 -- type F4GE0684G*D600 580 (Nm)

-- Maximum torque: model VL630 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL640 -- type F4GE0684E*D600 630 (Nm)

-- Maximum torque: model VL660 -- type F4GE0684C*D600 700 (Nm)

Maximumtorquespeed . 1400 rev/min

Numberofmainbearings . 5 7

Sump . steel

(continued)


SECTION 10 - ENGINE - CHAPTER 1 3

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Lubrication . forced, with gear pump

Pumpdrive . camshaft

Enginespeed/oilpumpspeedratio . 2:1

with mesh filter on oil intake and cartridge

Oilfiltering.

on delivery line

filter

Normal oil pressure with motor warmed--up

atslowidling. 10.15 psi (0.70 bar)

atfastidling . 50.76 psi (3.50 bar)

Cooling . coolant circulation

on mod. VM460 -- VM370 -- VL570 -- VL610 -- VL620

Radiator

VL630--VL640--VL660 . Engine coolant and hydraulic circuit fluid

--

Fan,drivenbyahydraulicmotor. suction, steel with 8 blades

Coolantpump.

Coolantthermometer .

Temperature ranges corresponding to each section:

-- greensector(normalconditionsofuse) .

-- redsector .

At 221 °F (105°C) every minute

Caution!

230 °F (110°C) every 10 seconds

under

centrifugal vane--type

with 12 segments

104 °F --212°F (40°C --100°C)

212 °F --248°F (100°C --120°C)

Enginespeed/coolantpumpspeedratio . 1:1,977

Temperaturecontrol . via thermostat valve

-- initialopening. 177.8 ± 35.6 °F (81± 2 °C)

system . overhead valves operated by tappets, rods

Timing

rocker arms via the camshaft located

and

Intake:

(cont)

the engine block; the camshaft is driven

in

the crankshaft using straight--tooth

by

gears

-- start:beforeT.D.C. . 15°

-- end:afterB.D.C. . 35°

Exhaust:

-- start:beforeB.D.C. . 69°

-- end:afterT.D.C. . 21°

Clearance between valves and rocker arms with engine cold:

-- intake ., PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. 0.009 ± 0.001 in. (0.25 ± 0.05 mm)

-- exhaust . 0.019 ± 0.001 in. (0.50 ± 0.05 mm)

For further timing system technical data . see page 12

(continued)

604.82.321.00 -02 - 2005


4 SECTION 10 - ENGINE - CHAPTER 1

GENERAL SPECIFICATIONS 4 cylinders 6 cylinders

Fuel system

with dual cartridge dry air filter, with

Airfiltering.

filter indicator

clogged

Fuelpump. with double diaphragm

. through wire filter in fuel supply pump, and

Fuelfiltering

cartridge on delivery line to

replaceable

604.82.321.00 -02- 2005

injection pump

Camoperated . engine timing

BOSCHinjectionpump. rotating distributor type

All--speed governor, incorporated in pump:

BOSCH . centrifugal counterweights

Automatic advance regulator, incorporated in pump:

BOSCH . hydraulic

For further fuel system technical data:

advance (pump setting for start of delivery before TDC)

Fixed

Pressure setting -- Injection order, and other information

--

. refer to the data for the relevant engine

regardingtheBOSCHpump

in the table on page 2

type

(cont)


Turbocharger:

SECTION 10 - ENGINE - CHAPTER 1 5

FUEL SYSTEM DATA

For version F4GE0484C*D601:

--

. GKB13L/A085BXL

--typeHOLSETHX27W

For versions F4GE0684C*D600 -- F4GE0684E*D600 --

--

F4GE0684G*D600:

--typeHOLSETHX35W .

E7735AG/E16XB11

. rotating distributor with speed governor

Injectionpump

advance regulator incorporated

and

BOSCH pump:

-- model VM460 -- VM370 -- VL570 -- type F4GE0484C*D601 VE 4/12 F 1150 L 956 -- 504053467

-- modelVL610--typeF4GE0684G*D600 . VE 6/12 F 1150 L 964 -- 504060083

-- modelVL620--typeF4GE0684G*D600 . VE 6/12 F 1150 L 964 -- 504060083

-- modelVL630--typeF4GE0684E*D600 . VE 6/12 F 1150 L 981 -- 504060084

-- modelVL640--typeF4GE0684E*D600 . VE 6/12 F 1150 L 981 -- 504060084

-- modelVL660--typeF4GE0684C*D600 . VE 6/12 F 1150 L 978 -- 504053466

Directionofrotation . anticlockwise

.

Injectionorder

modelVM460--VM370--VL570 . 1--3--4--2

--

-- mod.VL610--VL620--VL630--VL640--VL660 . 1--5--3--6--2--4

Fuel injectors:

BOSCHtype.

VM460

VM370

VL570

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. 504063465

F4GE0684E*D600

DSLA

P 1174

145

VL610

VL620

504063465

DSLA

145 P 1174

VL630

VL640

504063465

DSLA

145 P 1174

VL660

504063465

DSLA

145 P 1174

Numberofnozzleholes . 6 6 6 6

Nozzleholediameterin.(mm.) .

F4GE0484C*D601 -- F4GE0684C*D600 --

--

-- F4GE0684G*D600 .

F4GE0684E*D600

0.009

(0.223)

. 3771 to

Calibrationpressurepsi(bar)

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

0.009

(0.223)

to 3771

3974

(260 to 274)

604.82.321.00 -02 - 2005


6 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VM460 - VM370 - VL570 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 4/12 F 1150 L 956

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1150 0.091 -0.138

1.1

-3.5) (2.3

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1./2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 73.5 -79.5 cc/1000 0

Difference

cc/1000

700 103.5 -109.5 cc/1000 1000 3.5

1.4 Minimum 400 6.5--18.5 cc/1000 0 6.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1280 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(11.0--21.0) - (0 .3 -- 0.5 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1150

0.091--0.138 (2.3--3.5)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1280 max, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. 3.0 1000

p p p

Lever

-

-

1150 95.0--101.0 1000

700 103.5 -109.5 1000

700 88.0 -94.0 500

500 73.5 -79.5 0

Minimum 400 6.5--18.5 0

450 max. 3.0 0

curve 100 > 80.0 0

g Starting

300 < 93.5 0

-

-

-

--

--

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

-


SECTION 10 - ENGINE - CHAPTER 1 7

VL610 - VL620 - CALIBRATION DATA

MOD.

BOSCH INJECTION PUMP TYPE VE 6/12 F 1150 L 964

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

-- 380000228).

380001084

ASSEMBLY DIMENSIONS

SVS

SYMBOL

(max)

KF MS ya yb

mm - - - - -

1. CALIBRATION DATA

Rpm Values

Advance stroke 1000 0.063--0.110

1.1

-2.8) (1.6

CALIBRATION TEST CONDITIONS

bench conforming to ISO 4008/1./2

Test

conforming to ISO 7440--A61 --

Injectors

with calibrated pad ∅ 0.02 in.

(1.688.901.027

mm)).

(0.5

pressure setting 3581 to 3668 psi

Injector

to 253 bar).

(247

Fuel supply pressure: 5.072 psi (0.35 bar).

pipes (conforming to ISO 4093.2):

Delivery

x 0.0787 x 17.716 in. (mm 6 x 2 x 450).

0.236

liquid: ISO 4113 at a temperature of

Test

± 32.9 °F (55° ± 0.50 °C) at outlet.

131

in.

(mm)

1.2 Supply pressure - - bar --

Max. delivery

1.3

pressure

without

Max. delivery

1.3

pressure

with

L.D.A.

hPa

1000

500 86.2 -92.2 cc/1000 0

Difference

cc/1000

700 80.8 -86.8 cc/1000 1000 3.5

1.4 Minimum 360 7.0--23.0 cc/1000 0 5.0

1.5 Starting 100 > 80.0 cc/1000 0

1.6 Peak speed 1290 max. 3.0 cc/1000 1000

1.7 Start of delivery 1150 Delivery difference Advance difference

depending on load 1000 hPa -(6.0--16.0) - (0 .4 -- 0.6 )

2.1 Advance

LDA=1200 hPa

2.2 Supply pressure

LDA=1200 hPa

Backflow

LDA=1200 hPa

Rpm

in. (mm)

Rpm

bar

Rpm

cc/10 sec

2. TEST VALUES

KSB=0 Volt 1000

0.063--0.11 (1.6--2.8)

KSB=0 Volt -

2.3 Delivery Rpm cc/1000 hPa

on peak speed stop 1290 max. 3.0 1000

p p p

Lever

-

-

1150 75.0 -81.0 1000

900 80.8 -86.8 1000

500 92.5 -98.5 325

500 86.2 -92.2 0

Minimum 360 7.0--23.0 0

420 max. 3.0 0

curve 100 > 80.0 0

g Starting

250 < 107.0 0

-

-

-

1150

2.1--3.3

--

--

KSB=12 Volt 100

>3.0

KSB=12 Volt -

604.82.321.00 -02 - 2005

-


8 SECTION 10 - ENGINE - CHAPTER 1

604.82.321.00 -02- 2005

VL630 - VL640 - CALIBRATION DATA

MODD.

BOSCH INJECTION PUMP TYPE VE 6/12 F 1150 L 981

FOR

DATA

ASSEMBLY

timing on engine: delivery start 0° ± 1° before

Pump

of cylinder 1 on compression stroke.

T.D.C.

pre--lift for pump timing on en-

Plunger

0.0393 in. (1 mm) from B.D.C. (with tools

gine:

Источник: [https://torrent-igruha.org/3551-portal.html]

MONDAY, OCTOBER 20, 2014   9:00-17:00

POSTER PLUS VIDEO I – Poster Exhibition – Hall XL__________

P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN; COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY

N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1, S. Date1, J. Bapaye3

1Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale Medical College, Pune, India

Contact E-mail Address:[email protected]

INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis. The best approach for drainage of these collections is still controversial. We present our retrospective data comparing the two endoscopic methods for drainage of WOPN.

AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural drainage (EUTMD) using a newly designed fully covered large-bore wide-flare metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who underwent placement of multiple plastic stents (Gr II). The pre-op CECT confirmed suitability of endoscopic drainage based on location, wall thickness & contents. Visual quantification of necrosis (>50% solid debris) by EUS excluded 8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by standard technique by a single endoscopist. The difference between the two groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of NCT and subsequent necrosectomy was done whenever necessary. Follow-up imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes were compared in terms of clinical success, need for surgery, complications, hospital stay and mortality.

RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of demographics, etiology of pancreatitis, cyst location, size and amount of debris. Placement of NCT, need of necrosectomy and no of sessions required were also not different between the two groups. Clinical success defined as resolution of symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p = 0.048). None of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II (p = 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p = 0.016)

Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p = 0.012). Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p = 0.22)

CONCLUSION: The Nagi stent™ is effective and safe for EUTMD of WOPN. It permits rapid clinical resolution with 100% technical and clinical success rates. It offers distinct advantage over plastic stents although further prospective studies are warranted.

Disclosure of Interest: None declared

P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF THE ESOPHAGUS USING A “RENDEZ-VOUS” TECHNIQUE

J.-M. Gonzalez1,*, G. Vanbiervliet2, M, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Barthet1

1Gastroenterology, Aix-Marseille University, North Hospital, Marseille, 2Gastroenterology, Nice Hospital, Nice, France

INTRODUCTION: Complete esophageal obstruction leads to definitive fasting. The rendez-vous endoscopic approach had already been described for complex stenoses as an alternative to surgery that has high morbid-mortality.

AIMS & METHODS: This is a case series report about six patients referred for complete esophageal disruption classified in two groups: 1/ Long disruption (> 5cm), one after caustic ingestion and two due to an esophageal stripping during SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (< 5cm), consecutive to radiation therapy for a neck neoplasia. They had been fasting for 3 to 18 months. All the procedures were performed according the anterograde retrograde approach, under anesthesia and with CO2 insufflation and X-rays guidance.

RESULTS: There were 3 men and women between 25 and 71 years old. All the reconstructions have been successful in one to three endoscopic sessions, using the non hydrophilic tip of a guide wire passed through a straight catheter in 5 cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created, by transillumination (n = 1) or head and neck surgery (n = 1). In order to guide the reconstruction, SEMS was used in one case, NGT in one case, and both were used in one patient. The first dilation was performed with a CRE balloon (12-15mm). All the patients could eat mixed after 2 POD. There was no intra-operative or post-operative complication. Then, the patients underwent 3 to 18 dilations sessions during 1.5 to 15 months; two are still undergoing dilations and all eat normally.

CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe and effective in case of esophageal disruption even with loss of SES, avoiding surgery.

Disclosure of Interest: None declared

P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY GASTRIC CANCERS USING THE CLUTCH CUTTER

K. Akahoshi1,*, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Y. Motomura1, M, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Kubokawa1, J. Gibo1, N. Kinoshita1, S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1, N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1

1Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: To reduce the risk of complications related to ESD using conventional knives, we developed the Clutch Cutter (CC), which can grasp and incise the targeted tissue using electrosurgical current.

AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients (228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intramucosal or superficial submucosal gastric cancer without lymph node involvement, that had been confirmed by preliminary endoscopy, EUS, and endoscopic biopsies, were enrolled into this prospective study. The CC was used for all steps of ESD (marking, circumferential marginal incision, submucosal dissection, and hemostatic treatment). The therapeutic efficacy and safety were assessed.

RESULTS: The mean size of the early gastric cancers and resected specimens was 17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes. The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respectively. The R0 resection rates according to tumor size and location were 97.4% (229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9% (127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/95) in upper portion. The mean operating time according to tumor size and location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9 min in lower portion, 108.8 min in middle portion, and 117.2 min in upper portion. Perforation during ESD occurred in one case (0.3%), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully treated by endoscopic hemostatic treatment.

CONCLUSION: ESD using CC is a safe and technically efficient method for resecting early gastric cancers.

REFERENCES

1) Akahoshi K, Akahane H, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Murata A, et al. Endoscopic submucosal dissection using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.

2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic submucosal dissection using the clutch cutter for early stage digestive tract tumors. Digestion 2012: 85: 80-84.

Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM have applied for the patent in Japan, Europe, and USA for the Clutch Cutter described in this article. China has already ownload gom player full version Archives the patent., Y. Motomura: None declared, M. Kubokawa: None declared, J. Gibo: None declared, N. Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T. Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya: None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M. Oya: None declared

P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS

M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Ponchon5

1Gastroenterology and endoscopy, Hôpital Edouard Herriot, 2Inserm U1032, 3Functional disorders unit, Hôpital Edouard Herriot, Lyon, France, 4Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania, 5Gastroenterology and endoscopy unit, Hôpital Edouard Herriot, Lyon, France

Contact E-mail Address:[email protected]

INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising method for the treatment of the esophageal achalasia. But the precise technique can be refined. We developed a combined technique of water jet system for tunnelling and hook knife section for myotomy and we evaluated its results in a prospective study.

AIMS & METHODS: The patients presented with an achalasia without any prior instrumental treatment. The submucosal tunnel was created 12 cm over the cardia and 3 cm below, and then the endoscopic myotomy was performed using the Olympus Hook Knife by a single operator with CO2 insufflation, beginning 8 cms over the cardia and finishing 2 cms below. The clinical evaluation was realized before and then after the procedure at 1, 3, 6 and 12 months (score of Eckardt, score of quality of life GIQLI). A high-resolution manometry was realized before POEM and 3 months later to classify the achalasia (classification of Chicago) and to measure basal pressure and pressure of relaxation integrated (PRI) of the lower esophageal sphincter. Then an esophageal pHmetry of 24 hours was performed at 3 months to diagnose GERD. The data are expressed in median (extremes) and compared before and later myotomie by paired t-test.

RESULTS: 21 patients (13 men, average age 61 years) were included. 18 procedures were complete, 1 was not realized because of a large esophageal diverticulum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries occurred but did not prevent to continue the procedure after mucosal closure by clips. Dual Knife ® (n = 7) or the water jet Nestis Enki 2 ® (n = 11) were used for the tunnel. No mucosal injuries were observed with the water-jet system. Hook Knife ® was used for all myotomies. The average time of procedure was 94.2 min with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated with a needle during the procedure in 13 cases without any visible perforation. CT scan at day 1 showed a pneumomediastinum (n = 14/18), a pneumoperitoneum (n = 14/18) and/or a peumothorax (n = 3/18). No sepsis was observed. Feeding was always possible with liquids at day 1. All patients noted a clinical improvement. At 3 months, the basal pressure of the SIO was decreased for all patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p<0.01) as well as the PRI (8 mmHg (0-16) against 23 mmHg (9-28), p<0.01). pH metry showed a pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases.

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CONCLUSION: Water-jet injection allows rapid and safe tunneling of the submucosa and myotomy with hook knife is very precise. Safety and effectiveness of mytomy is reinforced using these technical refinements.

Disclosure of Interest: None declared

P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGH-MAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY FOR DIFFERENTIATION OF GASTRIC LESIONS

R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3, E. Nikonov4, V. Kapranov5, A. Rusakov6

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation, 2Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic №1 of the Business Administration for the President of Russian Federation, Moscow, 5Internet Center, 6Administration, P. G. Demidov Yaroslavl State University, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: High-magnification endoscopy with narrow-band imaging (HME-NBI) has been used for diagnosis of gastric pathology because of its high accuracy. Nevertheless, the application of these advanced techniques in clinical practice is difficult due to the presence of various histological changes of gastric mucosa with different modifications of microvascular and microsurface patterns. Newly developed computer-aided decision support systems are designed to detect and/or classify abnormalities and thus assist a medical expert in improving the accuracy of medical diagnosis. However, there is lack of data for computer-aided devices for classification of gastric lesions with HME-NBI.

AIMS & METHODS: The aim of this study was to evaluate the effectiveness of computer-aided classifier of endoscopic magnification images of gastric lesions. We analyzed our database contains 78 endoscopy NBI magnification images of gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images were classified into three classes: oval (13 images), tubular (31 images), and destroyed with vessel network (34 images). Initially we divided images of every class into two sets — training set and test set. Then we selected uniformly distributed random points with fixed density (one random point for every 300 pixels) at every picture, which were analyzed by extracting topological features for building the classifier. Training set images were used for classifier training with Adaboost algorithm and testing set images of each group were utilized for testing with previously trained classifier. We repeated the procedure described above for the estimation of classifier quality.

RESULTS: From 78 database images there were 50 images (66.6%) with the success rate of correct classification exceeding 80%. In 14 images (17.9%) all points (100%) were recognized correctly. The mean percentage of points with the correct classification was 79%.

CONCLUSION: Topological features were successfully used for description of endoscopic magnification images. The combination of topological features analyzed with Adaboost algorithm allowed for creating and effective training of computer-aided Web Site Express 2.6.3.035 crack serial keygen of endoscopic magnification images of gastric lesions.

Disclosure of Interest: None declared

P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS CONDITIONS AND LESIONS OF THE STOMACH

R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3

1Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration, Polyclinic №1 of the Business Administration for the President of the Russian Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation

Contact E-mail Address:[email protected]_veavuk

INTRODUCTION: Endoscopic mapping of the entire stomach with advanced techniques has been recommended as an important step of surveillance of premalignant gastric conditions/lesions [1]. Although current imaging technologies, such as narrow-band imaging (NBI) and high-magnification endoscopy, allow enhanced visualization of gastric mucosa, their application is still limited due to low contrast and brightness of endoscopic view and complexity of usage. Newly developed NBI system with dual focus (DF) magnification might be a promising tool to overcome this challenge.

AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy of new NBI-DF system in detection, characterization of gastric lesions in patients with extensive atrophy and/or luxonix purity vsti v1 metaplasia. A total of 43 patients (mean age 51.3 years, SD = 12.1) were initially examined by conventional white light endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy (CE) with indigocarmine was performed as the “gold standard” for detection of lesions. Any suspicious areas detected by NBI or CE were subsequently further assessed with NBI with DF (Olympus Exera III GIF H190) and characterized accordingly. Biopsies were taken from all lesions for histological assessment.

RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic (chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 high-grade dysplasia/early gastric cancer. All lesions (100%) detected by CE were found with NBI observation. Endoscopic histology prediction was successful in 88 cases (94.6%) Endoscopic misdiagnosis was found in 5 PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen (5.4%): overestimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive predictive value and Native Instruments - Kontakt Factory Library v1.3.0 | Download Torrent predictive value were 80%, 97.4%, 85.7% and 96.2% respectively for early gastric cancer/high-grade dysplasia.

CONCLUSION: Observation of gastric mucosa with a novel NBI system was at least as effective as CE with indigocarmine in detection of suspicious gastric lesions in patients with precancerous conditions and lesions of the stomach. Dual focus magnification provides sufficient assessment of microvascular and microsurface patterns in order to differentiate gastric lesions. Further randomized controlled studies are needed to be performed for clarifying the role of novel endoscopic system in diagnosis of gastric pathology.

REFERENCES

1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.

Disclosure of Interest: None declared

P0007 DEVELOPMENT OF A PROTOTYPE OF VIDEO SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES DURING ENDOSCOPIC EVALUATION OF BARRETT’S OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL STUDY

S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1

1CHU Strasbourg, 2IRCAD, Strasbourg, France

Contact E-mail Address:[email protected]

INTRODUCTION: The prevalence of Barrett's oesophagus (BE) is 5 to 6% in the general population, with a progression from dysplasia to adenocarcinoma 0.6 to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early lesions accessible to endoscopic treatment. However, the relocalisation of lesions detected by biopsies may be difficult during follow-up endoscopies. The purpose of this study was to evaluate the prototype of a magnetic probe for accurate location of the position of the endoscope, allowing the relocalisation of this position in a subsequent endoscopy. We report the results of a feasibility study in pigs and the use of this device in two patients with BE.

AIMS & METHODS: The system consists of an electromagnetic (EM) field transmitter and an EM probe constituting the electromagnetic tracking system (EMS) (NDI, Aurora). The EM probe is inserted through the operating channel of a double channel gastroscope. The EM field generator is positioned on the patient's chest wall. The system also includes new software developed at IHU/IRCAD, which performs simultaneous recording of the video from the endoscope alongwith Web Design Archives - Download Pro Crack Software corresponding position, as measured by the EMS. During a second endoscopy, this software allows automatic synchronisation of the recorded video to provide relocalisation of the endoscope in front of previous biopsy sites in the oesophagus.

The system was tested in 5 anesthetised pigs. During the first endoscopy, ten markings were performed by argon plasma electrocoagulation (ERBE Tübingen, Germany) in the distal oesophagus. The position of each marking was recorded by the system. A second operator to then performed a blind endoscopy on the same pigs and was asked to follow the system implicitly as a guide to relocate the markings.

In 2 patients with BE, the system was then tested to facilitate relocalisation of the biopsy sites.

RESULTS: Ten markings were made in the distal oeosphagus of 5. After withdrawal of the endoscope the second operator found 48 of the 50 markings (96%) using the guidance provided by the system. The positioning of the endoscope provided by the EMS system was within a 2mm range from the initial positionning. In the VSDC Video Editor Pro 6.8.1.336 Crack 2021 License Key of BE patients, the system relocalised the biospy sites within a range of 3mm.

CONCLUSION: This preliminary study shows the feasibility of the EMS prototype to relocalise the endoscope in the oesophagus within an acceptable range, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. The clinical usefulness of this system should be evaluated further during the follow-up of patients with BE.

Disclosure of Interest: None declared

P0008 THE UTILITY OF ROUTINE CHROMOENDOSCOPY FOR DETECTION OF DYSPLASTIC LESIONS DURING SURVEILLANCE COLONOSCOPY IN PATIENTS WITH PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen INFLAMMATORY BOWEL DISEASE. DOES RESEARCH TRANSLATE TO CLINICAL PRACTICE?

U. Javaid1, R. Thethi1, P. Luthra1, N. Mohammed2,*, J. Hamlin1, B. Rembacken1, V. Subramanian2

1Gastroenterology, St James University Hospital, Leeds Teaching Hospital NHS Trust, Deezer 6.2.36.2 Crack APK + Activation Code (2021), Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective studies to improve dysplasia detection rates by improving the ability to detect subtle mucosal changes. (1) The utility of CE in dysplasia detection in patients with IBD during routine clinical practice has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by CE with standard white light endoscopy (WLE).

AIMS & METHODS: Retrospective cohort study of patients with long standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching Hospital NHS Trust between January 2012 to December 2013. Details of diagnosis, duration of disease and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records and patient notes.

RESULTS: There were 120 colonoscopies in the CE group and 220 colonoscopies in the WLE group. The groups were well matched for all demographic variables. 27 dysplastic lesions were detected in 20 patients in the CE group and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the lesions were detected on targeted biopsy and IDM Crack 6.37 Build 7 Latest Version with Serial Keys Archives low grade dysplasia. The adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic lesion was 4.6 (95% CI 1.6-13.7) in favour of CE.

CONCLUSION: CE colonoscopy improves detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD even in routine clinical practice, confirming data from prospective trials. CE should be the standard of care for all IBD surveillance procedures as advocated by both BSG and ECCO guidelines.

REFERENCES

(1) Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33: 304-312.

Disclosure of Interest: None declared

MONDAY, OCTOBER 20, 2014   9:00-17:00

LIVER & BILIARY I – Poster Exhibition – Hall XL__________

P0009 INVOLVEMENT OF B-CELLS IN HEPATIC INFLAMMATION DURING NONALCOHOLIC STEATO-HEPATITIS (NASH)

A. Jindal1,*, S. Sutti1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1 on behalf of Laboratory of General Pathology, Prof. Albano, Novara, Italy

1Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Growing evidence indicates that adaptive immunity contributes to the process leading to chronic hepatic inflammation in NASH. However, the mechanisms involved are still incompletely characterized. Recently, B-lymphocytes have emerged as players in orchestrating adipose tissue inflammation in obesity contributing to the development of insulin resistance.

AIMS & METHODS: We investigated the possible role of B-cell responses in the pathogenesis of NASH. NASH was induced by feeding four weeks C57BL/6 mice with a methionine-choline deficient (MCD) diet.

RESULTS: In mice receiving the MCD diet the development of steatohepatitis was associated with an increased hepatic infiltration by B220 (CD20) positive B-lymphocytes and by the detection of circulating IgG targeting oxidative stress-derived antigens such as malonildialdehyde- (MDA) and 4-hydroxynonenal-protein adducts. Moreover, immunohistochemistry showed the presence of IgG deposits within the hepatic inflammatory infiltrates that co-localized with MDA-derived antigens, indicating the formation of immunocomplexes. To substantiate the role of oxidative stress in triggering B-cell responses in NASH, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen were immunized with MDA-adducted bovine serum albumin (MDA-BSA) before feeding the MCD diet. In MCD-fed, but not in control mice, MDA-BSA immunization promoted liver B-cell expansion and enhanced transaminase release, lobular inflammation and the hepatic production of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-12. Among immunized MCD-fed mice there were also positive correlations between the individual expression of the B-cell marker B220 and those of macrophage M1 activation markers IL-12p40 and iNOS (r = 0.87 and 0.71 respectively; p<0.02).

This effect was likely mediated by B-cell interaction with CD4 T-cells as in the same animals B220 expression also positively correlated with that of IFN-γ (r = 0.76; p<0.03) and of the co-stimulatory molecule CD40 (r = 0.72; p<0.05). Furthermore, depleting CD4+ T-cells in MCD-fed immunized mice by using an anti-CD4 monoclonal IgG did not affected B220 expression, but significantly lowered the hepatic mRNAs IFN-γ, iNOS and IL-12p40 and ameliorated lobular inflammation and focal necrosis.

CONCLUSION: These results indicate that B-cell responses triggered by oxidative stress can contribute to inflammation in NASH by stimulating T-cellular responses.

Disclosure of Interest: None declared

P0010 GENERATION OF A VECTOR CONTAINING AN SHRNA FOR THE RECEPTOR CB1 AS AN ANTIFIBROGENIC STRATEGY IN LIVER DISEASE

A. Díaz Rivera1,*, V. Chagoya de Sánchez 2, G. Velasco Loyden 2, L. García Benavides 3, J. Armendáriz Borunda 1, A. Sandoval Rodríguez1

1Molecular Biology and Gene Therapy Institute, Guadalajara, 2Cellular Physiology Institute, México, D. F, 3Institute of Experimental and Clinical Therapeutics, Guadalajara, Mexico

Contact E-mail Address:[email protected]

INTRODUCTION: Blockade of cannabinoid type I receptor (CB1) by pharmacological antagonist has demonstrated antifibrogenic effects in models of cirrhosis. Gene therapy with a shRNA molecule for CB1 wthinin an adenovirus has the advantage of hepatic tropism, which will reduce side effects and increase the transduction efficiency.

AIMS & METHODS: Design a shRNA that efficiently inhibit the expression of CB1, evaluate its antifibrogenic effect in an experimental model of liver cirrhosis and generate an adenoviral vector coding for the shRNA-CB1.

shRNA sequences were designed to blockade mRNA of CB1 at positions 877, 1232, 1501 (pshCB1-A, B, D). The effectiveness of the shRNA was evaluated by inhibition of the mRNA-CB1 after transfection of the plasmids in primary culture rHSC. To determine the optimum dose for transfection in primary cultures, lipofectamine 2000 and Fugene ® HD were tested using a GFP expressing plasmid (pITR-GFP). Later, we evaluated shRNA mediated-CB1 inhibition in cirrhotic rats intoxicated with CCl4. The plasmids were administrated by hydrodynamic injection in a volume of 4 mL. Then, in animals transfected with the most potent shRNA-CB1, mRNA levels of fibrogenic molecules (TGF-β1, Col 1 and α-SMA) and percentage of fibrotic liver tissue was measured. Finally, Ad5 backbone coding for shRNACB1-1232 or shRNA-Irrelevant was generated by homologous recombination between pshRNA and the pAd / BLOCK-iT ™ DEST.

RESULTS: In vitro shRNA designed to block position 877 and 1232 significantly inhibited mRNA (p> 0.05) CB1 gene expression in 77% and 91%, respectively using Fugene ® HD. The sequence of shRNA-Irrelevant did not affect mRNA expression of CB1. Hydrodynamics-based transfection of shRNA-CB1 via iliac vein in the rat allows efficient and repeatable delivery to the liver. A volume of 4 mL carrying 3 mg/kg was administered in 5-7 seconds. In CCl4 model shCB1-1232 showed major decrease in CB1 mRNA and protein (p<0.05), and in consequence fibrogenic molecules TGF-β1, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Col I, α-SMA also reduced (60%, 47% and 77% (p<0.05); respectively). Fibrosis diminished 49% (p<0.05) compared to untreated controls. Thus pshRNACB1-1232 was selected for production of adenovector. Homologous recombination between attL and attR regions between pshRNA-1232-CB1 and pAd / BLOCK-iT ™ DEST allowed the generation of Ad-shRNA1232-CB1 backbone.

CONCLUSION: shCB1-1232 demonstrates CB1 gene and protein silencing in vitro and in vivo, decreasing mRNA levels of key fibrogenic molecules and fibrosis, showing potential to be used as therapeutic strategy for liver fibrosis. Recombinant adenovirus expressing this shRNA will have the advantage of high titers production conserving efficient liver transduction, which will facilitate its therapeutic application in experimental models of liver cirrhosis or even clinical scenarios.

Disclosure of Interest: None declared

P0011 CORRELATION BETWEEN INDIRECT SERUM MARKERS AND MORPHOMETRIC VALUES OF FIBROTIC TISSUE IN PBC

C. Stasi1,*, L, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Leoncini1, M.R. Biagini1, S. Madiai1, F. Marra1, G. Laffi1, S. Milani2

1Department of Experimental and Clinical Medicine, 2Department of Biomedical, Experimental and Clinical sciences, University of Florence, Florence, Italy

INTRODUCTION: The accuracy of non-invasive methods for the quantification of liver fibrosis in patients with PBC is still debated. Moreover, the Ludwig’s PBC stages do not represent a measurement of quantitative fibrosis.

AIMS & METHODS: We determined the histomorphometrical measurement of fibrotic tissue and analyzed the accuracy of a number of indirect markers of liver fibrosis for the detection of different histological stages of PBC and the association between indirect serum markers and morphometric values (MV) of fibrotic tissue.

Methods: Sections of liver tissue were stained with hematoxylin/eosin and

Sirius red. Only samples with a > 25 mm length and including at least 11 complete portal tracts were considered adequate for the study. Histomorphometrical measurement of fibrotic tissue was performed on sirius red stained sections of liver biopsies. Area percentage measures of fibrotic tissue were ranked into 4 groups reflecting Ludwig’s staging and compared with values of the following serum markers of liver fibrosis: APRI, LOK, FORNS, FIB-4. The percentage of fibrosis was calculated with ImageJ. All results were expressed as mean ± standard deviation. The numerical comparison of continuous data was performed using the Wilcoxon signed ranks test applied to two-samples. Linear regression analysis between two variables was performed by using Pearson correlation. Statistical significance was set at a value of p<0.05.

RESULTS: We enrolled 50 patients with PBC (mean age, 57±12.30 years; 43 F and 7 M; 8 AMA negative, 42 AMA positive), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. There were 19 (38%) patients in Ludwig’s PBC stage I, 14 (28%) in stage II, 12 (24%) in stage III and 5 (10%) in stage IV. The morphometric values (Table 1) of fibrotic tissue were significantly different in the various Ludwig’s stages of PBC (p<0.05). Only LOK score was statistically different between stage II and III (p = 0.02). No other significant differences were found in the various Ludwig’s stages of PBC for APRI, FORNS, FIB-4 and LOK scores (Table 1). A statistically significant correlation was found between MV and Forns (R2 = 0.3643, p = 0.0004), MV and FIB-4 (R2 = 0.3945, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, p = 0.0002), MV and LOK (R2 = 0.3367, p = 0.0010), MV and APRI (R2 = 0.1476, p = 0.0361).

Table 1.

Ludwig's stagesMorphometric valuesFORNSFIB-4LOKAPRI
Stage I0.74% ± 0.653.61 ± 1.620.24 ± 0.260.20 ± 0.160.61 ± 0.76
Stage II3.87% ± 1.54.55 ± 1.80.35 ± 0.390.22 ± 0.180.49 ± 0.35
Stage III6.15% ± 1.685.52 ± 2.060.35 ± 0.160.38 ± 0.190.67 ± 0.44
Stage IV14.06% ± 8.458.05 ± 1.761.00 ± 0.760.69 ± 0.341.24 ± 0.79

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CONCLUSION: Histomorphometric values of fibrotic tissue increase progressively in Ludwig’s stages of PBC, where non-invasive markers do not, and correlate positively with indirect serum markers of liver fibrosis.

Disclosure of Interest: None declared

P0012 THE NGF RECEPTOR P75NTR LEADS TO NEURAL HYPERTROPHY DURING THE DEVELOPMENT OF LIVER CIRRHOSIS AND MALIGNANT LIVER TUMORS

D. Hartmann1,*, S. Werscher1, R. Göß1, S. Teller1, M. Schlitter2, K. Becker2, H. Friess1, G.O. Ceyhan1

1Department of Surgery, 2Institute of Pathology, Technische Universität München, Munich, Germany

Contact E-mail Address:[email protected]

INTRODUCTION: The autonomic nervous system is the involuntary part of the peripheral nervous system and regulates the intestinal motor activity, smooth muscles and exocrine glands. Autonomic nerves that innervate the liver reach the organ via the hepatic hilum and run together with the portal vein, the hepatic artery and the bile duct. In the full clinical picture of liver cirrhosis, no parenchymal innervation can be detected. In addition, malignant liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC), are not innervated.

AIMS & METHODS: The aim of this work is the characterization of a possible hepatic neuroplasticity, including responsible neurotrophic factors. In the present work, a collective consisting of 103 patients (22 patients with normal liver tissue, 23 patients with liver cirrhosis, 45 patients with HCC and 13 patients with CCC) was examined for variations in nerve number and nerve size. In addition, growth factors, such as Growth-Associated Protein (GAP-43) and Nerve Growth Factor (NGF), as well as their receptors TrkA and p75NTR were investigated by immunohistochemistry and qRT-PCR in terms of their involvement in a possible hepatic neuroplasticity.

RESULTS: The multiple comparison of median nerve sizes of the examined entities showed a clearly significant difference. The largest nerves were discovered in HCC samples. However, no difference in neural density was detected. Furthermore, significant differences were observed for the high affinity NGF-receptor TrkA and the low affinity NGF-receptor p75NTR with regards to immunoreactivity and relative expression. The highest p75NTR expression was found in normal liver tissue and both, relative expression as well as immuno-reactivity, decrease with increasing nerve size.

CONCLUSION: The results of the present study suggest that the observed neural changes in the liver are related to active neural remodeling processes. The NGF receptor p75NTR seems to take on a key role in this context. Since p75NTR binds all neurotrophins with low affinity, further research is warranted concerning its involvement in the plasticity of hepatic nerves.

Disclosure of Interest: None declared

P0013 HIGH CONCENTRATION OF FIBROTIC AND INFLAMMATORY MARKERS AMONG PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen WITH SCHISTOSOMAL LIVER DISEASES

E. Sinkala1,2, P. Kelly3,4, E. Sinkala1,2,*

1Internal Medicine, University of Zambia, 2Internal Medicine, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, TROPGAN, Lusaka, Zambia, 3Internal Medicine, Barts and London, Blizzard Institute, London, United Kingdom, 4Internal Medicine, University Teaching Hospital, Lusaka, Zambia, Lusaka, Zambia

Contact E-mail Address:[email protected]

INTRODUCTION: Worldwide the commonest cause of portal hypertension is cirrhosis, but in tropics it is schistosomiasis. Some parts of Zambia are hyper-endemic with prevalence of 77%. Hepatocellular function is preserved in hepatosplenic schistosomiasis hence prognosis is better than cirrhosis. Liver biopsy can confirm fibrosis but it is invasive.

AIMS & METHODS: This is an ongoing case control study involving 70 cases and 20 controls. All cases had varices and were negative for HIV, hepatitis B and C viruses. Hyaluran was used as a marker of liver fibrosis while TNF receptor 1, sCD14, IL1 beta, IL 6 and CRP were inflammatory markers.

We set out to investigate fibrotic and inflammatory makers in hepatosplenic schistosomiasis patients at the University Teaching Hospital, Lusaka, Zambia.

RESULTS: Eighty patients were evaluated and serology for schistosomiasis was positive in 74 (93%) and negative in 6 (7%). Hyaluran levels compared with controls were higher, p<0.001 (median 111.6ng/ml, IQR 39.1, 240.3). Inflammatory markers were elevated: TNF receptor 1 concentrations compared with controls were higher, p <0.001 (median 3150.1pg/ml (IQR 1703.2, 10460.0), sCD14 values were higher than in controls p<0.001, median 2365.0ng/ml (IQR1744.9, 3128.6). IL 1 beta values were higher than in controls p = 0.013, median 4.3pg/ml (IQR 0.8, 13.2) and so were IL 6 values p = 0.001 (median 15.26pg/ml, IQR 10.15, 38.13). Spearman’s rank correlation of hyaluran and TNF receptor 1 was positive (r = 0.44, p = 0.002) and so was hyaluran and IL6 (r = 0.251, p = 0.045).

CONCLUSION: Schistosomiasis is a leading cause of portal hypertension in Zambia and induces a liver fibrotic marker which could be used to assess disease severity. It seems hepatosplenic schistosomiasis also induces high levels of TNF receptor 1, sCD14, IL1 beta and IL6. These elevated markers could be due to bacterial translocation which needs to be confirmed by markers of bacterial translocation such as LPS.

Disclosure of Interest: None declared

P0014 LIVER FIBROSIS PREVENTION AFTER INTRAMUSCULAR ADMINISTRATION OF MATRIX METALLOPROTEINASE-8 ADENOVIRAL VECTOR IN A MODEL OF HEPATIC FIBROSIS

J. Garcia-Bañuelos1,*, E. Eden Oceguera-Contreras1, D. Gordillo-Bastidas1, A. Sandoval-Rodríguez1, B. Bastidas-Ramírez2, J. Gonzalez-Cuevas1, J. Macias-Barragan1, B, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Belinda Gomez-Meda1, J. Armendáriz-Borunda1 on behalf of INNOVARE, Guadalajara, Jalisco, México

1Instituto de Biología Molecular y Terapia Génica, Centro Universitario de Ciencias de la Salud, 2Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico

INTRODUCTION: MMP-8 degrades preferentially collagen type I (collagen of higher proportion of hepatic fibrosis). We delivered MMP-8 gene in to the muscle, using an Adenovirus vector, protein is released systemically and is activated in the liver.

AIMS & METHODS: Our aim was to evaluate profibrogenic gene expression pattern and liver fibrosis prevention.

We used four groups of rats (n = 15): control; thioacetamide (TAA), induced-fibrosis; TAA+AdGFP; TAA+AdMMP8. At the beginning of the fifth week of TAA intoxication, administration of vectors in soleum muscle was accomplished. Sub-groups of rats (n = 5) at the end of first, second and third week after vector administration were sacrificed. Percentage of fibrosis, liver function, gene expression of MMP8, proinflammatory genes (IL1-beta, TNF-alpha), profibrogenic genes (collagen α1(I), CTGF and TGF-beta) and antifibrogenic genes (MMP1 and MMP9), were determined.

RESULTS: After 3 weeks of treatment: In the liver and serum, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, amount of MMP8 protein was sustained, fibrosis decreased up to 48%, proinflammatory genes expression was modified only at the end of the third week, profibrogenic gene expression decreased (Col α1(I) 4 times, TGF-beta 3 times and CTGF 2 times), antifibrogenic genes expression increased (MMP9 2.8 times and MMP1 10 times). According to Knodell score, a clearly diminution of inflammatory cells infiltration in comparison with counterpart animals treated with AdGFP, could be appreciated.

CONCLUSION: A single dose of AdMMP8 in muscle is enough in order to obtain a stable liver MMP8 protein expression and activity during 21 days. Degradation of collagen in the liver modifies pro and anti-fibrogenic gene expression allowing TuneFab Spotify Music Converter 3.2.1 With Crack restoration of hepatic architecture.

Disclosure of Interest: None declared

P0015 WHOLE-PROTEIN MASS SPECTROMETRY TO IDENTIFY CONGENITAL DISEASE OF GLYCOSYLATION IN END-STAGE LIVER DISEASE

J.C. Jansen1,*, M.van Scherpenzeel2, D.J. Lefeber2, J.P. Drenth1

1Gastroenterology and Hepatology, 2Laboratory of Genetic, Endocrine and Metabolic Disease, Radboud University Medical Center, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Congenital disorders of glycosylation (CDG) are a heterogeneous group of autosomal recessive metabolic diseases with a wide spectrum of clinical symptoms. Depending on localization of the defective protein, two types are distinguished (CDG-I; endoplasmatic reticulum and CDG-II; Golgi apparatus). Liver involvement is frequent in both groups and can even be predominant for some CDG-II variants. Abnormal glycosylation is seen in liver cirrhosis, probably resulting from affected liver synthesis, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. We hypothesized that mass spectrometry (MS) differentiates between secondary and bonafide genetic causes in end-stage liver disease.

AIMS & METHODS: To determine the effect of a diminished liver function on glycosylation we analyzed anonymous serum samples drawn from end-stage liver disease patients prior to their liver transplantation. As a first step we used transferrin isoelectric focusing (tIEF) to detect abnormal glycosylation. Selected samples were further analyzed with transferrin whole-protein MS to obtain a comprehensive readout of the glycosylation profile.

We also obtained serum from 100 patients with a presumed CDG. Patients with a predominant liver phenotype were selected for further analysis using exome sequencing for identification of the pathogenic mutation.

RESULTS: We collected 1065 serum samples and found an abnormal tIEF pattern in 30%. All abnormalities were mild and resembled a CDG-II pattern. MS of abnormal tIEF samples had increased fucosylation of transferrin and loss of one sialic acid.

We identified 18 patients with a phenotype resembling Wilson disease with liver fibrosis, elevated transaminases, low ceruloplasmin and liver copper accumulation. DNA is currently prioritized for exome sequencing. MS comparison of the Wilson disease-like patients and liver transplant patients showed that desialization is more abundant in Wilson disease-like patients and transferrin fucosylation is seen more often in liver transplant patients.

CONCLUSION: Whole protein MS enables differentiation between abnormal glycosylation secondary to liver failure and bonafide CDG. This can aid in the detection of CDG as a cause for liver pathology.

Disclosure of Interest: None declared

P0016 MICRORNA EXPRESSION PROFILE IN SIMPLE STEATOSIS AND NON-ALCOHOLIC STEATOHEPATITIS

K. Okamoto1,*, T. Okamoto1, T. Onoyama1, K. Miyoshi1, M. Kishina1, J. Kato1, S. Tokunaga1, T. Sugihara1, Y. Hara2, M. Koda1, K. Hino2, Y. Murawaki1

12nd. Dept. of Internal Medicine, Tottori Univ. School of Medicine, Yonago, 2Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are regarded as histological subtypes of non-alcoholic fatty liver disease (NAFLD). The distinctive pathological difference between SS and NASH is that NASH induces chronic liver inflammation and fibrogenesis, which can lead to liver cirrhosis. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression by repressing translation or degrading target mRNAs. Accumulating evidence indicates that miRNAs play important roles in various life functions including inflammation, metabolism, and fibrosis.

AIMS & METHODS: The purpose of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans. DD Shionogi PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Fatty Liver Shionogi (FLS), and FLS ob/ob mice were subjected as the normal control, SS model, and NASH model, respectively. Microarray analysis was used to assess 375 miRNA expression profiles in mouse liver tissue. Normalized miRNA expression ratios over ±2log2 between FLS and FLS ob/ob were identified as candidates. Real time PCR was used to check the reproducibility of the microarrays predicting miRNAs from 4 mice in each group. The putative miRNA target genes were predicted using the web-driven software DIANA microT-CDS. DAVID 6.7 was used to perform gene ontology annotation and KEGG pathway enrichment analysis. The putative miRNA expression profiles in human serum were also examined in every 10 patients with asymptomatic gallbladder stones, SS, and NASH.

RESULTS: In microarray analysis, 18 miRNAs were identified as candidates. Among the 18 miRNAs, 6 showed good expression ratio reproducibility in real time PCR and were confirmed to express commonly between mice and humans. The expression levels of miR-200a and miR-200b increased in the order of normal control, SS, and NASH. miR-1 was downregulated in NASH. miR-376c, miR-409, and miR-411 showed potent high expression in SS, over 30-fold of DS. KEGG pathway analysis indicated that the strongly expressed miRNAs in SS (miR-376c, miR-409, and miR-411) had multiple targets in the TGF-β signaling pathway including TGFR, smad 2, 3, and 4. The analysis suggests that miR-376c, miR-409, and miR-411 may protect liver fibrosis through silencing the TGF-β signaling pathway. In human serum, hierarchical clustering analysis of the putative miRNA expression also showed clearly different expression profiles between SS and NASH.

CONCLUSION: The expression profiles of 6 miRNAs were different between SS and NASH models. Some potential target genes of the putative miRNAs were found to be involved in the TGF-β signaling pathway. Furthermore, the putative miRNA expression profiles in human serum were also clearly different between SS and NASH patients. These miRNAs have high potential as biomarkers to distinguish the fate of NAFLD patients and contribute to further research in the pathogenesis and treatment of NASH.

Disclosure of Interest: None declared

P0017 PROTECTIVE EFFECTS OF MELATONIN ON THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS

K. Celinski1,*, G. Czechowska 1, A. Korolczuk2, G, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Wójcicka3, J. Dudka4, A. Bojarska-Junak5, A. Mądro1, H. Cichoż-Lach1

1Gastroenterology, 2Department of Clinical Pathomorphology, 3Department of Clinical Pathophysiology, 4Medical Biology, 5Clinical Immunology, MEDICAL UNIVERSITY OF LUBLIN, Lublin, Poland

Contact E-mail Address:[email protected]

INTRODUCTION: The aim of the present study was to determine the effect of melatonin on liver fibrosis induced with long-term administration of thioacetamide (TAA) in an animal model. The antifibrotic effects of melatonin were assessed by determining activity indirect markers of fibrosis, i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and direct markers represented by proinflammatory cytokines such as interleukin 6 (IL-6), interleukin beta 1 (IL-beta1), tumour necrosis PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen alpha (TNF-alpha, transforming growth factor beta 1 (TGF-beta1) and platelet-derived growth factor (PDGF- AB). Moreover, parameters of oxidative stress were determined, i.e. concentrations of oxidised glutathione (GSSG) and reduced glutathione (GSH), activity of paraoxonase 1 (PON-1), an enzyme of antioxidative properties. Inflammatory changes and extent of fibrosis were evaluated histologically.

AIMS & METHODS: Experiments were carried out in Wistar rats. Animals were divided into 4 groups, 8 individuals each: group I- controls receiving drinking water ad libitum for 12 weeks, group II – TAA, 300 mg/L ad libitum for 12 weeks, group III- melatonin, 10 mg/kg b.w. administered intraperitoneally (IP) daily for 4 weeks, group IV – TAA, 300 mg/L ad libitum for 12 weeks followed by melatonin, 10 mg/kg/b.w. administered IP daily for 4 weeks.

RESULTS: Results of serum determinations demonstrated significantly lower activity of AST, ALT and AP in the group receiving TAA followed by melatonin (IV) compared to the group receiving only TAA (II). Immunoenzymatic findings regarding the effect of melatonin on concentration of proinflammatory cytokines (Il-6, Il-beta1, TNF-alpha, TGF-beta 1, PDGF-AB) confirmed these data.

CONCLUSION: Biochemical examinations in liver homogenates revealed statistically significant improvement of oxidative stress parameters (concentration of GSH increases and concentration of GSSG decreases) in animals with TAA-induced liver damage receiving melatonin (IV). Moreover, the activity of PON-1 toward phenyl acetate and paraoxon was found to be increased in liver homogenates and serum in the group receiving TAA followed by melatonin (IV) compared to the TAA group (II). Microscopic evaluation disclosed inhibitory effects of melatonin on inflammatory changes and extent of liver fibrosis.

Disclosure of Interest: None declared

P0018 ROLE OF GAMMA-KETOALDEHYDES AS NOVEL MEDIATORS OF EXPERIMENTAL FIBROGENESIS AND STELLATE CELLS ACTIVATION

L. Longato1,*, K. Rombouts1, D. Dhar1, S. Davies2, J. Roberts2, T. V. Luong1, M. Pinzani1, K. Moore1

1UCL Institute for Liver & Digestive Health, University College London, London, United Kingdom, 2Pharmacology, Vanderbilt University, Nashville, United States

Contact E-mail Address:[email protected]

INTRODUCTION: Reactive lipid aldehydes formed during lipid oxidation such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSCs) to a pro-fibrogenic phenotype. γ-Ketoaldehydes (γ-KAs) are highly reactive lipid aldehydes formed during oxidation of arachidonic acid or as a by-product of the cyclo-oxygenase pathway. γ-Ketoaldehydes are ∼100x more reactive than HNE, and form protein adducts and cross-links. Increased circulating concentrations of proteins cross-linked to γ-ketoaldehydes are present in patients with alcoholic liver disease.

AIMS & METHODS: The aim of this study was to investigate whether one specific γ-ketoaldehyde, namely levuglandin E2 (LGE2), can induce activation of HSCs. Cultured activated, serum-starved primary mouse and human HSCs were exposed to various concentrations (0.5 pM-5 µM) of levuglandin E2 (LGE2) for up to 48 hours. Endpoints measured included proliferation (BrdU incorporation), cytotoxicity (lactate dehydrogenase (LDH) release and tetrazolium (MTS) reduction), RNA expression (qRT-PCR), protein expression (Western Blot), and collagen secretion in conditioned medium (SirCol assay).

RESULTS: HSCs exposed to LGE2 exhibited profound cytotoxicity at 5 μM concentration, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, as indicated by LDH leakage and reduced MTS. This was mediated by an induction of apoptosis, indicated by an increase in PARP cleavage, occurring as early as 8 hours after LGE2 exposure. However, at lower, non-cytotoxic doses (ranging from 50 pM-500 nM, with a maximum effect observed at 0.5 nM), LGE2 promoted HSC activation as indicated by increased expression of α-smooth muscle actin and vimentin, as well as increased proliferation and collagen secretion. In addition, LGE2 exposure promoted sustained activation of signalling pathways, as indicated by the increased phosphorylation of the kinases ERK1/2 and JNK, as well as an increase in mRNA levels of chemokines such as IL-8 and MCP-1. We are currently investigating the potential protective action of administration of a γ-ketoaldehyde scavenger in an animal model of hepatic fibrosis.

CONCLUSION: γ-Ketoaldehydes represent a newly identified class of activators of HSCs in vitro, which are biologically active at concentrations as low as 50 pM.

Disclosure of Interest: None declared

P0019 NONINVASIVE SERUM FIBROSIS MARKERS IN COMPARISON WITH GRADING AND STAGING IN CHRONIC HEPATITIS

M. Abdollahi1,*, A. Pouri2, M. Somi2

1Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, 2Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Islamic Republic Of

Contact E-mail Address:[email protected]

INTRODUCTION: Chronic hepatitis is defined as a necroinflammatory disease of the liver continuing for at least six months. The aim of this study was to evaluate the role of noninvasive fibrosis markers by assessing the association among grading and staging and these diagnostic parameters in patients with chronic hepatitis.

AIMS & METHODS: We retrospectively studied 221 patients with chronic hepatitis between 2011 and 2013. Routine biochemical indices and serum fibrosis indexes such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were determined, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Receiver operating characteristic curve (ROC) analysis was conducted to compare diagnostic accuracies of these markers for prediction of significant fibrosis.

RESULTS: We identified 221 liver biopsies from chronic hepatitis patients with contemporaneous laboratory values for imputing AAR, APRI and FIB-4. From all, 135 males (61.1%) and 86 females (38.9%), with the mean age of 39.6±14.4 were studied. FIB-4, APRI and AAR were correlated significantly with the stage of fibrosis, with a higher correlation coefficient than other markers in the patients with Hepatitis B (r =  0.46), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, C (r =  0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) was superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy.

CONCLUSION: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Disclosure of Interest: None declared

P0020 REVEALING Octane render c4d torrent Archives MOLECULAR MECHANISM OF RAT LIVER RESPONSE TO LONG-TERM OMEPRAZOLE TREATMENT WITH BIOINFORMATICS APPROACH

S. Vakal1, E.A. Virag2, K. Dvorshchenko1, L. PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen "Institute of Biology", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, 2University of Pecs, Pecs, Hungary

Contact E-mail Address:[email protected]

INTRODUCTION: Omeprazole is a widely prescribed acid-suppressing drug available for clinical use for 25 years. Despite well-studied adverse effects of short-term omeprazole treatment, underlying mechanisms of some hepatotoxic effects of long-term injection of high omeprazole doses (e.g. development of oxidative stress and histopathologic changes [1]) are not understood. Transcriptome analysis is a powerful tool for elucidation of possible mechanisms of cellular response to different conditions on molecular level. Bioinformatics approach is suitable for processing of large datasets, prediction of possible regulatory circuits and generation of hypotheses on involved molecular mechanisms [2].

AIMS & METHODS: The purpose of the research was to find out possible molecular mechanisms of rat liver cells response to long-term injection of omeprazole.

GSE8858 dataset and GPL2454 platform description were downloaded from NCBI Genome Expression Omnibus database. Gene expression data from livers of rats treated with 30 mg/kg and 415 mg/kg for 1 and 25 days were compared in order to reveal differentially expressed genes (DEGs). DEGs were determined with GEO2R tool on the basis of t-criterion and adjusted p value. Gene ontology (GO), pathway enrichment analyses and building of protein-protein interactions (PPI) network were performed with STRING 9.1. Prediction of miRNAs and cis-elements for DEGs was carried out with WebGestalt toolkit. Clusters were identified by K-means analysis in ClusterONE. All networks were visualized using Cytoscape.

RESULTS: In total 79 DEGs (21 up- and 58 down-regulated) and 87 DEGs (41 up- and 46 down-regulated) were identified in samples of rat livers treated with 30 and 415 mg/kg during 25 days, respectively. At the same time 22 genes with similar pattern of expression (9 up- and 13 down-regulated) were found for both types of dosage. Among them are Arntl, Cdk1a, Chka, Gpam, Litaf, Slc2a5, Usp2 etc. Enrichment in such GO terms was revealed: cell cycle, mitosis, nuclear division, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, lipid metabolism. Only genes involved in lipid metabolism were up-regulated, while others were suppressed. Genes involved in PPAR signalling pathway were found to be differentially regulated upon 25-day treatment with omeprazole. Most of DEGs (51 genes) were of cytoplasmic proteins (housekeeping genes). PPI networks were constructed for 98 proteins and 102 interactions revealed. The optimal amount of clusters was equal to 3. MiRNA-9, 17-5p, 20A, 20B, 106A, 106B, 200B, 200C, 429, 506 and 519D were found to be involved in regulation of revealed DEGs. 24 probable cis-elements were predicted for promotors of identified DEGs.

CONCLUSION: Thus, long-term treatment of rats with omeprazole is associated with changes in expression of housekeeping genes: down-regulation of genes involved in cell-cycle process and cellular division, up-regulation of genes involved in lipid metabolism, and changes in expression of PPAR signalling pathway genes.

REFERENCES

1. Dvorshchenko KO, Bernyk OO, Dranytsyna AS, et al. Influence of oxidative stress on the level of PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen expression Tgfb1 and Hgf in rat liver upon long-term gastric hypochlorhydria and administration of multiprobiotic Symbiter. Ukr Biokhim Zh 2014; 85: 114-123.

2. Shen B, Zhou S, He Y, et al. Revealing the underlying mechanism of ischemia reperfusion injury using bioinformatics approach. Kidney Blood Press Res 2013; 38: 99-108.

Disclosure of Interest: None declared

P0021 MORPHOLOGICAL AND FUNCTIONAL CHANGES OF LIVER MACROPHAGES DURING THE PROGRESSION OF NONALCOHOLIC STEATOHEPATITIS (NASH)

S. Bruzzi'1,*, S. Sutti1, A. Jindal1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1

1Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: Recent reports indicate that both human and experimental NASH is characterized by an increase in hepatic monocyte infiltration and that macrophages have an important role in regulating the disease evolution. However, little is known about the functional changes occurring in liver macrophages during the progression of NASH.

AIMS & METHODS: NASH was induced in C57BL/6 mice by feeding a methionine-choline deficient (MCD) diet up to 8 weeks.

RESULTS: Mice receiving the MCD diet showed a progressive worsening of parenchymal damage and lobular inflammation, while liver fibrosis was evident only after 8 weeks of treatment. Hepatic F4/80-positive macrophages increased in parallel with the disease progression. In the early phases of NASH after 4 weeks on the MCD diet these cells prevalently expressed markers of inflammatory monocytes such as Ly6C and CD11b, but the prevalence of Ly6C+/CD11b+ cells decreased by extending the treatment up to 8 weeks. This paralleled with a lowering in the monocyte chemokines CCL1/CCL2 and their receptors CCR8/CCR2. We observed that the expression of the macrophage M1 activation markers iNOS and IL-12 also peaked at 4 weeks and declined thereafter. No appreciable changes were instead observed in the levels of M2 polarization markers arginase-1 and MGL-1, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Histology revealed that the macrophages accumulating in advanced NASH (8 weeks MCD) were enlarged, vacuolized and formed small aggregates. Immunofluorencesce showed that these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting that they have phagocytosed apoptotic bodies derived from dying fat-laden hepatocytes. At flow cytometry, enlarged macrophages were characterized by a weak Ly6C/CD11b expression and by a low IL-12 production. On the other hand, these cells showed an enhanced expression of the anti-inflammatory mediators IL-10 and annexin A1. The production of the pro-fibrogenic cytokine TGF-β was increased in the macrophages obtained from NASH livers, irrespective of the cell phenotype.

CONCLUSION: Altogether, these data indicate that during the progression of NASH liver macrophages down-modulate their pro-inflammatory phenotype in parallel with the phagocytosis of apoptotic hepatocytes and acquired anti-inflammatory properties.

This work has been supported by a grant from the Fondazione Cariplo (Milan).

Disclosure of Interest: None declared

P0022 MICRORNA-27B DEVELOP THE FATTY LIVER FORMATION AND INSULIN RESISTANCE AT THE SAME ONSET

T. Kessoku1,*, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Y. Honda1, Y. Ogawa1, K. Imajo1, Y. Eguchi2, K. Wada3, A. Nakajima1

1gastroenterology and hepatology, Yokohama city university, yokohama, 2internal medicine, saga university, saga, 3 Pharmacology, Osaka University Graduate School of Dentistry, Oosaka, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in Asia Pacific region is close to 12–24%, while in Western countries is about 20–30%1). And nonalcoholic fatty liver disease (NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. In spite of its high prevalence, up till now there is no proven effective treatment for NAFLD3). Along with the “obesity epidemic,” the worldwide prevalence of NAFLD is increasing rapidly and is generally assumed to be a consequence of obesity-induced insulin resistance 2). On the other hand, not all obese individuals are insulin resistant, nor are all insulin-resistant individuals obese 4). MicroRNAs (miRs) are a class of small non-coding RNAs that function to control gene expression by inducing the degradation or inhibiting the translation of mRNA through an association with its 3’-untranslated region (3’UTR). Although miRs play a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM), detailed mechanisms of this pathogenesis remain unclear.

AIMS & METHODS: We found that miR-27b increased in liver biopsy specimens of NAFLD patients with DM using microarray analysis, as compared with controls. The aim of this study was to investigate whether overexpression of miR-27b in liver could cause fatty liver formation and insulin resistance, and to examine the mechanism of NAFLD and DM onset in a murine model.

Five-week-old male C57BL/6J mice were randomized into 2 groups (n = 16 mice): basal diet (BD)-fed control mimic (BD-Con, n = 4), BD-fed miR-27b-mimic (BD-miR-27b, n = 4). In this study, miR-27b mimic is PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen intravenously at 7mg/kg. We comfirmed the target genes of miR-27b using quantitative RT-PCR analysis. Insulin serum concentrations were measured by a local laboratory for clinical examinations. As an alternative method for assessing insulin resistance (IR), the homeostasis model assessment of IR (HOMA-IR) was calculated using the PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen formula: fasting insulin (mU/mL) plasma glucose (mg/dL) / 405.

RESULTS: BD-miR-27b significantly showed steatosis using oil red o staining and increased hepatic tryglyceride content, as compared with BD-Con. In the analysis of fat accumulation-related gene expression, hepatic Peroxisome proliferator-activated receptor α (PPARα) and Microsomal triglyceride transfer protein (MTTP) are significantly decreased. At the same time, BD-miR-27b showed hyperinsulinemia and insulin resistance. In the analysis of insulin resistance-related gene expression, hepatic Insulin receptor substrate 1 (IRS-1) is significantly decreased.

CONCLUSION: miR-27b controls multiple gene levels that are involved in fat accumulation and insulin resistance, resulting in the NAFL and DM pathology. These results propose a therapeutic approach for NAFL and DM by targeting miR-27b.

REFERENCES

1) Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia–Pacific region: executive summary. J Gastroenterol Hepatol 2007; 22: 775–777.

2) Clark JM, Brancati FL and Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649–1657.

4) Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity: European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166–1173.

Disclosure of Interest: None declared

P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER REGENERATION IN A RABBIT MODEL

F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase future remnant liver volume in patients requiring extended Stellar Phoenix Video Repair Crack With Product Key Full Latest Version 2021. Reversible PVE is of interest when generating sufficient hypertrophy while preserving the embolized liver lobe. The concept of reversible PVE requires an absorbable embolization material.

AIMS & METHODS: The aim of this study is to modulate lysis time of a fibrin-glue based embolization material while using different concentrations of Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG.

PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5 groups:

• Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, n = 4)

• Fibrin glue with Aprotinin (FG700KIU, n = 5)

• Fibrin glue with Aprotinin (FG500KIU, n = 5)

• Fibrin glue with Aprotinin (FG300KIU, n = 5)

• Fibrin glue without Aprotinin (FG-Aprot, n = 5)

The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight ratio of NEL were evaluated.

RESULTS: Data were compared with a previous series using a permanent embolization material, i.e. polyvinyl alcohol + coils (PVAc), showing complete and permanent occlusion of the embolized portal vein branch in all rabbits after 7 days.

FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of the FG+1000KIU Aprotinin group was still occluded and showed a hypertrophy response comparable to the PVAc group. The group of FG 700KIU Aprotinin survived 14 days and in two of the five rabbits, the embolized PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen vein was recanalized at sacrifice. The hypertrophy response in these rabbits was not different from the PVAc group. The rabbits with FG 500KIU and 300KIU Aprotinin were sacrificed at day 49, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. In the group with FG 500KIU Aprotinin, 4 out of 5 showed recanalization of the cranial portal branches. In the group with FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups showed hypertrophy response rates not different compared to the PVAc group.

CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU Aprotinin resulted in 70% reversible embolization with a hypertrophy response comparable to the PVAc group.

Disclosure of Interest: None declared

P0024 TRANSPLANTATION OF HUMAN AMNION-DERIVED MESENCHYMAL STEM CELLS AMELIORATES CARBON TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS

K. Kubo1,*, S. Ohnishi1, N. Sakamoto1

1Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease caused by a variety of factors, such as viral infections, alcohol, drugs and chemical toxicity. The only effective available treatment for end stage liver fibrosis is transplantation; however, due to the lack of donors, complications and transplant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs) have been reported to be a valuable cell source in cell therapy. Recently, bone marrow- or adipose tissue-derived MSCs have been reported to be effective in the treatment of liver fibrosis. In addition, several studies have shown that MSCs can be easily isolated from human amnion, and a large amount of cells can be obtained. Therefore, we examined the effects of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.

AIMS & METHODS: All pregnant women gave written informed consent, and amnion was obtained at Cesarean delivery. hAMSCs were isolated by collagenase treatment, and expanded with culture medium containing fetal bovine serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a week for 7 weeks. At 3 weeks, hAMSCs (1×106 cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative RT-PCR were performed.

RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area and deposition of type I collagen. In addition, hAMSC transplantation significantly decreased the number of α-SMA-positive hepatic stellite cells and and CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expression of α-SMA was significantly decreased in the liver of hAMSC-treated rats, and mRNA expression of type I collagen, TGF-β and IL-1β tended to be decreased by hAMSC transplantation.

CONCLUSION: Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through inhibition of inflammatory reaction. hAMSC would be considered as a new cell source for the treatment of liver fibrosis.

Disclosure of Interest: None declared

P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER CELLS IN AN ANIMAL MODEL OF NAFLD

V. Lembo1,*, G. Mazzone1, G. D'Argenio1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine and Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most common liver disease in Western countries, is pathogenetically related to a sedentary lifestyle as well as to poor quality diet characterized by an excessive energy intake including high fatty foods and high amounts of fructose, the so-called Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of triglycerides. Vitamin D in addition to the effects on lipid metabolism, plays other biological functions, among which a trophic effect on human cultured cells.

AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by Western Diet, the relationship between body weight, liver weight and grade of steatosis; and if these parameters are modified by vitamin D supplementation. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD); WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment was conducted for 6 months. Weekly, the rats, body weight was recorded. At sacrifice, livers were excised and weighed and samples were stored at -80°C. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis was numerically scored following semi-quantitative pathological standard.

RESULTS: During the experiment the increase of body weight was similar in the three groups. In the two groups fed with WD liver weight How to Download significantly higher than SD group (p<0.01). A positive correlation between body weight and liver weight was observed in WD groups (p<0.0001). The liver/body weight ratio was significantly higher in WD and WDVitD groups than SD: 2.9±0.05, 2.8±0.07 and 2.0±0.04, respectively; p<0.001). Steatosis was present in 61% and 21% of hepatocytes in WD group and WDVitD group, respectively, and absent in SD group. No correlation was found between the grade of steatosis and liver or body weight nor between the grade of steatosis and liver/body weight ratio. Although vitamin D supplementation reduced the degree of steatosis, liver/body weight ratio in WDVitD group was similar to WD group.

CONCLUSION: In a rat model of NAFLD induced by WD the presence and extent of steatosis are independent from body weight. Interestingly and unexpectedly, in WD groups the supplementation with vitamin D reduces liver steatosis but not liver weight: this sustains the hypothesis of a trophic effect of vitamin D on liver cells.

Disclosure of Interest: None declared

P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT MODEL OF NAFL

G. Mazzone1,*, V. Lembo1, G. D'Argenio1, M. Guarino1, M. D'Armiento2, F. Morisco1, N. Caporaso1

1Department of Clinical Medicine PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen Surgery, 2Department of Advanced Biomedical Science, University of Naples Federico II, Napoli, Italy

Contact E-mail Address:[email protected]

INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease (NAFLD) rise to become the most common cause of chronic liver disease in Western countries. It is known that insulin resistance and type 2 diabetes mellitus (T2DM) have an important role in the pathogenesis of obesity and NAFLD. A growing body of evidence points to a linked and potentially causative relationship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.

AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin D3 supplementation is able to modulate the liver effects and glucose homeostasis of a westernized diet, high in fat and fructose, in an animal model of NAFL without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23 IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6 months. Liver histology was examined by haematoxylin/eosin and Oil Red-O staining. Insulin resistance was determined according to the Homeostasis Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evaluated according to Brunt EM et al.

RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while in WDVitD group only 27% of hepatocytes contained fat. In WD group HOMA-IR was significantly higher than in SD (41.9±8.9 vs 6.17±1.3, p<0.01) and it was reduced by vitamin D supplementation in WDVitD group (41.9±8.9 vs 19.4±5.2, p<0.05). Interestingly SD and WDVitD rats were not diabetic (98.7±8.0 and 103.2±6.1, respectively) while all rats in WD group were diabetic (139±9.6) with glycemic values significantly higher than SD (p<0.01) and WDVitD (p<0.05).

CONCLUSION: These results suggest that a daily supplementation of vitamin D3 is able to improve insulin sensitivity and to prevent the development of diabetes and hepatic steatosis in WD rats.

Disclosure of Interest: None declared

P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE

S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3, H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1

1Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research Center for Post-genome Science and Technology, 4Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Sphingomyelin (SM) is a major component in lipid microdomains, and SM is synthesized from ceramide by the action of SM synthase (SMS). We have recently reported that mice deficient for SMS2 are resistant to high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem 2011:286;28544). In this study, we examined the relationship between SM and ceramide molecular species and the development of NAFLD and insulin resistance in human.

AIMS & METHODS: Non-alcoholic students of our university with body mass index (BMI) ≥ 35 kg/m2 at the regular physical checkup in 2013 were enrolled, and volunteer students with BMI of 20-22 kg/m2 were set as a control group. Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0, C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver enzymes, lipids and insulin resistance were measured by blood examination. Abdominal ultrasound was performed to confirm the existence of fatty liver, and body composition including percent body fat (PBF) was measured by bioimpedance analysis.

RESULTS: The levels of total SM and ceramide were not altered in obese group (19-28 y.o., n = 12), compared with control group (18-27 y.o., n = 11). The concentrations of SM C18:0 and C24:0 in the obesity group were significantly higher than in the control group. Moreover, in the obese group, SM C20:0 and C22:0 tended to be higher than in PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen control group. In the analysis of total 23 cases, the serum levels of SM containing saturated fatty acids positively correlated with PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing unsaturated acyl chain and almost all ceramide species did not correlate with those items.

CONCLUSION: The present study demonstrated that the serum levels of SM species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are correlated with liver function and insulin resistance, suggesting that distinct SM species are involved in the development of NAFLD and insulin resistance.

Disclosure of Interest: None declared

P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18 AND CONTROLLED ATTENUATION PARAMETER (CAP) IN HEALTHY POPULATION

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutrição e metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative for the diagnosis of NAFLD, especially NASH.

AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy individuals with and without steatosis. Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis compared with US and CAP was assessed using AUROC.

RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass index) were 52.6±17.1 years and 28.2±4.9 kg/m2, respectively; 25% had a normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis on ultrasound was 52.1%.

The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respectively. Median CK-18 were elevated in patients with vs. without hepatic steatosis by ultrasound: 33.4 [IQR: 25–151] vs. 73.7 [IQR: 25–508] U/L, p <0.0001.

CK-18 significantly correlated with steatosis (ρ = 0.40), ALT (ρ = 0.40), CAP (ρ = 0.38), triglyceride (ρ = 0.32), waist circumference (ρ = 0.30), Tag Archives: Clip Studio Paint 2021 Crack (ρ = -0.28), AST (ρ = 0.27), LDL (ρ = 0.26), total cholesterol (ρ = 0.21) and the number of metabolic syndrome criteria (ρ = 0.29), but not with LSM or BMI.

The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of 243 dB/m) were 0.78 (95% CI = 0.71–0.86) and 0.74 (95% CI = 0.65–0.82), respectively.

CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151, with a very large range. It showed a good discriminating capacity for diagnosing steatosis.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI) AND ULTRASOUND

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, A. Carvalho3, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, Portugal

INTRODUCTION: The fatty liver index (FLI) derived from an Italian population includes serum triglycerides, serum gamma-glutamyltransferase, body mass index (BMI) and waist circumference. It has been used as a noninvasive measure of hepatic steatosis (HS), but has not been widely validated and not examined PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen the Portuguese population.

AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult population by fatty liver index (FLI) and correlate with the ultrasound findings; validate FLI for prediction of fatty liver in the Portuguese population.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI. Performance of FLI for diagnosing steatosis compared with US was assessed using AUROC.

RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circumference and BMIs were 50.5±18.4 years, 94.4±12.7 cm and 26.9±4.7 kg/m2, respectively; 43% were overweight and 22% were obese. The median of FLI was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.

Using the FLI, 27.6% of subjects had HS (FLI > 60), 41.8% had no HS (FLI < 30) and 30.6% were not classifiable (FLI 30-60), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. However, these cut-offs proposed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI <30 exhibited HS on ultrasound and 13.4% of subjects with FLI > 60 showed no steatosis. For the FLI, the area under the ROC curve was 0.88 for the diagnosis of HS.

There was a significant correlation (p < 0.01) between the FLI and the following variables: weight (ρ = 0.80), waist circumference (ρ = 0.74), presence of steatosis (ρ = 0.65), triglycerides (ρ = 0.58), BMI (ρ = 0.51), ALT (ρ = 0.43), GGT (ρ = 0.39), HDL (ρ = -0.36), age (ρ = 0.33), female sex (ρ = -0.33), insulin (ρ = 0.29), AST (ρ = 0.28), LDL (ρ = 0.24) and total cholesterol (ρ = 0.22). No correlation was found with physical activity.

CONCLUSION: FLI could accurately identify hepatic steatosis in the general Portuguese population. The calculation of FLI may be useful to suggest the possibility of the presence of steatosis and indicate the need for an abdominal ultrasound.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0030 “NORMAL” CONTROLLED ATTENUATION PARAMETER (CAP) VALUES: A POPULATION-BASED Loaris Trojan Remover 3.1.83 Crack + Activation Key Download OF HEALTHY SUBJECTS

S. Carvalhana1,2, J. Leitão3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*

1Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutrição e Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA, Lisbon, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen steatosis, based on transient elastography. The normal range of controlled CAP values needs to be explored in clinical and anthropometrically diverse healthy subjects. A recent study has shown an association of CAP with BMI and the number of metabolic syndrome criteria.

AIMS & METHODS: Aim: define the normal range of CAP values in healthy subjects and evaluate the associated factors.

Methods: Recruitment from a prospective epidemiological study of the general Portuguese adult population. CAP was performed using Fibroscan in 134 healthy subjects, without fatty liver on ultrasonography or positivity serology for HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.

RESULTS: From 134 consecutive individuals studied (66 males), 4 were excluded due to failure/unreliable liver stiffness measurements (LSM). The mean age and BMIs (body mass index) were 46.9±18.0 years and 24.9±3.5 kg/m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were obese. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3 dB/m, respectively. Men had a higher mean CAP value than women (mean±SD: 213.1±47.1 dB/m versus 191.8±47.8 dB/m, respectively; p = 0.012).

CAP significantly correlated with gender (ρ = 0.22), age (ρ = 0.22), waist circumference (ρ = 0.33), BMI (ρ = 0.22), alcohol consumption (ρ = 0.25), systolic blood pressure (ρ = 0.27), ALT (ρ = 0.27), fasting glucose (ρ = 0.24) and the number of metabolic syndrome criteria.

After allowance for potential confounders, CAP was not independently associated with BMI or other risk factors for nonalcoholic fatty liver disease.

CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy subjects and is not associated with BMI or the number of metabolic syndrome criteria.

Support: Cerega/SPG; Bolsa APEF, Roche Farmacêutica; Gilead Sciences

Disclosure of Interest: None declared

P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL

T.J. G. Gevers1,*, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4, J.P. Drenth1

1Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology, 4Nephrology, RadboudUMC, Nijmegen, Netherlands

Contact E-mail Address:[email protected]

INTRODUCTION: Several trials have demonstrated that somatostatin analogues decrease liver volume in mixed populations of patients with autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and possibly enhances risk for adverse events.

AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial) was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We excluded patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2. Primary outcome was change in liver volume, secondary outcomes were changes in kidney volume, eGFR, symptom relief and health-related quality of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within-group differences.

RESULTS: We included 43 ADPKD patients with polycystic liver disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver volume decreased from 4,859 ml to 4.595 ml (-3.1%;p<0.001), and median kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p = 0.006). eGFR declined 3.5% after the first injection and remained stable up to study end. Lanreotide significantly relieved postprandial fullness, shortness of breath and abdominal distension, but had no effect on any of the EuroQol-5D dimensions. Three participants had a suspected episode of hepatic or renal cyst infection during the study.

CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting lanreotide, but stabilized thereafter.

Disclosure of Interest: None declared

P0032 THE EFFECTS OF POLY-UNSATURATED FATTY ACIDS (PUFAS) IN A RODENT NUTRITIONAL MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)

V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1

14th Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

INTRODUCTION: NAFLD and subsequent NASH are probably the most common chronic liver diseases in western countries and have a high risk of development of liver cirrhosis associated Category Archives: VST high morbidity and mortality.

AIMS & METHODS: The aim of the study was to determine effects of administration of PUFAs in the MCD dietary model of NASH and to assess the potential anti-inflammatory role of PUFAs in the pathogenesis of NASH.

For 6 weeks were male mice fed either with MCD or with chow. There were 4 groups of animals. Both experimental and control groups received from the beginning either PUFAs or saline. Detailed liver histology, serum biochemistry, total lipid and fatty acids compound, adiponectin and leptin levels were determined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were measured.

RESULTS: Feeding with MCD resulted in histopathological changes of NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP). Administration of PUFAs led to significant Redshift Render 3.0.52 Crack For C4D/3ds Max [MAYA + Torrent] of total animal and liver weight in MP. PUFAs also decreased cholesterol levels (P<0.001), ALT (P<0.01) and AST levels (P<0.01). MP developed significantly less pro-inflammatory cytokine profile, had lower leptin (P<0.01) and higher adiponectin levels (P<0.01) than controls, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Administration of PUFA led also to lower serum concentrations of saturated and monounsaturated FA and to higher serum concentrations of polyunsaturated FA in MP. Total lipid content of liver was significantly lower in MP.

CONCLUSION: We conclude that PUFAs may play a causal role in the pathophysiology of NASH. In summary, PUFAs have favorable effects on histopathological changes, serum markers of liver damage, fatty acid compound and show anti-inflammatory properties. We expect that PUFAs may represent a promising way in prevention and treatment of this increasingly common disorder.

Disclosure of Interest: None declared

P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

W, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1, Y. Liu1,*

1Department of Gastroenterology, 2Institute of Clinical Molecular Biology & Central Laboratory, Peking University People's Hospital, Beijing, China

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized by a broad spectrum of hepatic pathology that is closely linked to obesity and ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and even cirrhosis. NAFLD is recently believed to be under the influence of the gut microbiota, which may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein.

AIMS & METHODS: We explored the composition of gut bacterial communities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina next-generation sequencing.

RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that most of the microbiota samples were clustered by disease status. Differences were abundant at phylum, family, and genus levels between NAFLD and healthy subjects. Lentisphaerae at phylum level was significant higher in NAFLD microbiota. Among those taxa with greater than 0.1% average representation in all samples, five genera including Alistipes and Prevotella were the genus types exhibiting significant higher level in healthy microbiota, while genera Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in NAFLD microbiota. In addition, lymphocyte profiles (CD4+T cell and CD8+T cell) and proinflammatory cytokines (TNF-α, IL-6 and IFN-γ) in gut biopsies of patients and healthy controls was analyzed to monitor the inflammation caused by dysbiosis microbiota. The levels of CD4+ T cells and CD8+ T cells were lower in NAFLD patients compared with healthy subjects, and the proinflammation cytokine TNF-α, IL-6 and IFN-γ showed high level in NAFLD patients. What was more, irregular arrangements of microvilli and widening of the tight junction were observed in gut mucosa of the NAFLD patients by transmission electron microscope.

CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD microbiota, decreased numbers of CD4+T cells and CD8+T cells, and increased levels of TNF-α, IL-6 and IFN-γ in gut mucosa of NAFLD patients suggest a role for gut microbiota in the gut inflammation and the dysregulated gut immunity, which promote pathogenesis of NAFLD. We postulate that the distinct composition of the gut microbiome among NAFLD and healthy controls could offer a target for intervention or a marker for disease.

REFERENCES

1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab 2013; 24: 537-545.

2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-127.

Disclosure of Interest: None declared

P0034 ASCITIC FLUID LACTOFERRIN FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS

A.A. Ghweil1,*

1TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY OF MEDICINE EGYPT, Qena, Egypt

Contact E-mail Address:[email protected]

INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This procedure is operator-dependent and lysis of PMNs during transport to the laboratory may lead PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen false-negative results. Furthermore, ascitic fluid culture is insensitive and leads to delays in diagnosis. The aim of this study was to assess the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to identify a cut-off level that can be used for future development of a rapid bedside test.

AIMS & METHODS: Sixty ascites samples from cirrhotic patients were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC concentrations were determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or greater with or without a positive culture was used for diagnosis of SBP.

RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/mL; compared with non-SBP samples (median, 39 ng/mL P < .001). The sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%, respectively. The area under the receiver operating characteristic curve was 0.98. Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis

CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis of SBP, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis.

Disclosure of Interest: None declared

P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS

C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D. I. Gheonea1, I. Rogoveanu1

1Gastroenterology, UMF CRAIOVA, Craiova, Romania

Contact E-mail Address:moc.li[email protected]

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex treatable malignancies as its management is dependent on the stage of the underlying condition – liver cirrhosis. An early diagnosis assures best curative chances, as liver resection or transplantation have good survival rates in the general population. Computer aided diagnostic and prognosis (CADP) models are currently being developed for a number of malignancies to help clinicians manage cases based on individual needs of the patients rather than general statistics.

AIMS & METHODS: Our aim was to develop a CADP based on our previous work involving artificial neural networks (ANN) [1] for successfully diagnosing early HCC cases and better prognosticate their evolution, based on a set of criteria in accordance with current guidelines.

Ethical clearance was obtained from the local board and 107 consecutive patients with previously diagnosed liver cirrhosis signed informed consents for entering the study, between January 2009 and February 2010. Clinical and demographic parameters (age, sex, body mass index, waist circumference, type of viral infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein thrombosis, size and number of possible tumors), elastography data (strain ratio, complexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular second moment, correlation) and stiffness value (FibroScan) were collected and imputed in the CADP. For patients with clear liver tumors contrast-enhanced ultrasound was performed and time-intensity curve parameters were calculated and fed to the ANN system: peak enhancement, time to peak, rise time, fall time, mean transit time, area under the curve. We have followed the 4-year incidence of HCC patients in tumor-free cases and assessed the evolution when any formation, either regeneration nodule or early HCC was found.

RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules [median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm (min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per patient: 1 (min: 1, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration nodules based on clinical, laboratory and imaging data. A total of 28 patients also developed HCC in the four-year follow-up period; the system correctly predicted high possibility for HCC occurrence in 26 of these patients (92.85%), while giving high estimates for HCC in another 16 patients that remained cancer-free until Stellar Data Recovery 10.1.0.0 With Crack Free Download 2021 We could successfully predict the rate of malignancy in cirrhotic patients by using a novel CADP system. We believe that such tools may become worthy aids to clinical management of patients with various types of digestive pathologies.

REFERENCES

1. Streba CT, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, et al. Using contrast-enhanced ultrasonography time-intensity curves as classifiers in neural network diagnosis of focal liver lesions. World J Gastroenterol 2012; 18: 4427–4434.

Disclosure of Interest: None declared

P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE COHORT STUDY

F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4, B. Sean2

1Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal, 2Intensive Care, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, 3Transplantation, University of Alberta, Edmonton, Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal

Contact E-mail Address:[email protected]

INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease (MELD) score ≥40 have high risk of death without liver transplant (LT). This study aimed to evaluate these patients’ outcomes after transplant.

AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic patients who underwent LT at one Canadian center between 2002 and 2012. Primary exposure was severity of end-stage liver disease measured by MELD score at transplant (≥40 vs. <40). Primary outcome was duration of first intensive care unit (ICU) stay after LT. Secondary outcomes were duration of first hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival rates.

RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score ≥40. These patients had longer first ICU stay after LT (14 vs. 2 days; p <0.001). MELD score ≥40 at transplant was independently associated with first ICU stay after transplant ≥10 days (OR, 3.21). These patients had longer first hospital stay after LT (45 vs. 18 days; p <0.001); however, there was no significant difference in the rate of ICU readmission (18% vs. 22%; p = 0.58) or re-transplant rate Mixcraft 9 Crack Pro Studio With Registration Code 2021 [Latest] vs. 4%; p = 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and 5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no significant difference in cumulative survival stratified by MELD score ≥40 vs. <40 at transplant (p = 0.59).

CONCLUSION: Cirrhotic patients with MELD score ≥40 at transplant utilize greater postoperative health resources; however, derive similar long-term survival benefit with LT.

REFERENCES

Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062.

Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation in patients achieving a model for end-stage liver disease score of PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen or higher. Transplantation 2013; 95: 507-512.

Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients. Crit Care 2010; 14: R117.

Disclosure of Interest: None declared

P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT STUDY

J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2, N. O'Connell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4

1Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust, Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI, University of Warwick, Coventry, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: There is a quest for biomarker discovery in liver disease especially to detect cirrhosis at an early stage. Current methods are invasive, more often requiring a liver biopsy to confirm the diagnosis. For patients with Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst generally helpful, is unable to confirm the presence of fibrosis particularly in the presence of fat within the liver which is inevitable in most cases with NASH.

The gut microbiome is altered in several gastrointestinal disorders, resulting in Sniper 3D Assassin 3.27.5 + Hack + Mod (Latest Version) Full Download 2021 gut fermentation patterns, which we (and others) have been able to recognise by analysis of volatile organic compounds (VOC) in urine, breath and faeces1. The altered structure of the small intestinal mucosa and increased gut permeability (noted in liver disease), we hypothesised, would also change the microbiome, hence recognisable by its unique “fermentome” pattern, making NASH distinguishable from controls.

AIMS & METHODS: To determine if NASH results in an altered VOC pattern in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguishable from cirrhotics vs non-cirrhotics.

33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8 with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and 12 controls (normal synthetic liver function). Urine was collected and 10 ml aliquots were stored frozen in universal containers. For assay, the containers were first heated to 40 ± 0.1oC. The headspace (the air above the sample) was then pumped from the containers and analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used for initial statistical evaluation, with a re-classification using a “leave one out” for calculating sensitivity and specificity.

RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in these different groups of liver disease. The control group was significantly different to all of the other groups with a sensitivity of 100%. Of the disease groups, NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively with specificity of 80%. NAFLD however had sensitivity of 50% but specificity of 80%.

CONCLUSION: This pilot study suggests the IMS (FAIMS – technology) offers a novel non-invasive approach to separate not only NASH from controls but also those with established cirrhosis using urine. It offers the potential for early non-invasive tracking of NASH and its complications.

REFERENCES

1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diagnostic modalities in gastroenterology – gas phase volatile compound biomarker detection. Aliment Pharmacol Ther 2014; 39: 780-789.

Disclosure of Interest: None declared

P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES

N. Ding1,*

1Gastroenterology, St Vincent's Hospital, Melbourne, Australia

Contact E-mail Address:[email protected]

INTRODUCTION: Endoscopic screening PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen gastro-oesophageal varices (GOV) is currently recommended for all cirrhotic patients. Noninvasive methods for liver fibrosis assessment are identifying increasing numbers of patients with “cirrhosis-range” liver stiffness measurements (LSM), increasing the number of referrals for screening endoscopy. The identification of simple non-invasive markers for the presence/absence of large gastroesophageal varices (GOV) would be clinically useful. We evaluated the performance of liver stiffness measurement (LSM) ± platelet count to identify the presence of large GOV in patients with Child Pugh (CP) A cirrhosis.

AIMS & METHODS: Data were collected retrospectively. The presence of cirrhosis was defined by LSM > 13.6 kPa using elastography. We performed a database search for patients with LSM > 13.6 kPa who underwent screening gastroscopy (2010 – 2013). Only patients with compensated liver disease were included. Large GOV were defined by diameter > 5mm or the PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen of high risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the combination of these factors to identify patients with large GOV. A training set of 71 patients was used, and results were validated using a second cohort of 201 patients from two independent centres.

RESULTS: The combination of LSM and Pl was more accurate for identifying CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs. 0.78 [0.66 – 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk score was 0.11 (Sens = 0.88, Spec = 0.77, PPV = 0.33, NPV = 0.98, accuracy = 78%). Results in the validation cohort confirmed the discriminatory power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically relevant cut-offs to improve the negative predictive value (NPV) for large GOV. The NPV for the combination of LSM < 25 kPa and Pl ≥ 100 and was 100% in both the training cohort and validation cohort. 82 (42%) of patients overall met this criteria.

CONCLUSION: The combination of LSM < 25 kPa and Pl ≥ 100 can be used to identify patients with compensated cirrhosis who Download revoice pro crack Archives not have large GOV. These patients do not benefit from endoscopic screening, but could be followed with annual LSM and full blood count.

REFERENCES

1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 1997.

2. de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53: 762–768.

3, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144, 102–111.e1.

4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement using Fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164–170.

Disclosure of Interest: None declared

P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN LABEL STUDY DATA

C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1, E. Berni3, C.J. Currie1

1Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff, 2Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United Kingdom

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of cirrhosis. In recurrent, overt, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent episodes.

AIMS & METHODS: The aim of this study was to characterise the impact of the number of prior HE episodes on the risk of future HE episodes. A post-hoc analysis was carried out Tweaknow Powerpack 5.1.0 Features Key: data from 322 patients with a history of HE from a phase 3, open-label study evaluating the long-term safety and tolerability of rifaximin-α 550mg BID. All eligible patients had a Conn score of 0–2 at enrolment, and had either successfully participated in a previous HE study with rifaximin-α (RFHE3001), or they were new patients enrolled with ≥1 verifiable episode of HE within the preceding 12 months.

RESULTS: 319 of 322 patients (647 observations) aged ≥18 years had all the information required for analysis. Median duration of follow-up was 17 months (IQR 8.9–25.4). Stratifying patient observations by number of prior HE episodes and using the Kaplan Meier method the probability of being event free at year one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and 0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539 (0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for 'one', 'two', ‘three’ and ‘four or more' prior HE episodes, respectively. Plotting the Kaplan Meier curves of time to next HE episode, stratified by the number of prior HE episodes, a clear association between decreased time to next HE episode and increased number of prior episodes was seen. Using log-rank tests, there was no significant difference between the survival curves of one prior and two prior HE episodes (χ2 = 0 on 1 degree of freedom (d.f.), p = 0.899), however there were significant differences between survival curves of one prior or two prior episodes and greater numbers of prior episodes (χ2 = 72 on 3 d.f., p<0.001).

CONCLUSION: This study supports the current understanding of the natural history of end-stage encephalopathy; as the number of prior HE episodes increased, the risk of subsequent HE episodes increased.

Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other: Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni Consultancy for: Norgine, C. Currie Consultancy for: Norgine

P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS AND PORTAL HYPERTENSION

P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1, J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on behalf of Vienna Hepatic Hemodynamic Lab

1Dept, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

Contact E-mail Address:[email protected]

INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repeatable tool to assess liver fibrosis and portal hypertension (HVPG). PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, new quality criteria for TE measurements have been proposed (Boursier et al. Hepatology 2013): very reliable: IQR/M <0.1; reliable: IQR 0.1–0.3, or IQR/M >0.3 if TE <7.1 kPa; poor reliable: IQR/M >0.3 if TE >7.1 kPa.

AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE measurements according to these new quality criteria (accurate = very reliable + reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal hypertension. Therefore we retrospectively identified patients undergoing TE, HVPG measurement and liver biopsy within 3 months at our tertiary care center.

RESULTS: Among 278 patients (48.7±13.1 years, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, 74.7% male, 75.7% viral etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate LS measurements (23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional or new criteria were all significantly and similarly strong correlated with fibrosis stage (R = 0.648 vs. R = 0.636) and HVPG (R = 0.836 vs. R = 0.846). The accuracy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% for traditional and new TE criteria, respectively. The positive (PPV) and negative (NPV) values for new criteria PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen the 14.5 kPa cut-off were 83% and 70%. For predicting HVPG ≥10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and 89.8% using traditional or new criteria, respectively. Both criteria resulted in AUCs for diagnosis of HVPG ≥10mmHg of over 0.95 with a PPV and NPV of 76% and 97%, respectively.

CONCLUSION: Applying new quality criteria for TE measurements significantly increases the number of valid TE measurements without affecting accuracy of TE for diagnosis of liver cirrhosis and portal hypertension.

Disclosure of Interest: None declared

P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL ENDOSCOPY

S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernández-Sordo'1, J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1, I. PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Guha1

1Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham, UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical Catholic University of Chile, Santiago, Chile

INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD) remains the gold standard test to screen for oesophageal varices (OV) in patients with liver cirrhosis. However, it has many limitations in terms of costs, accessibility and tolerability. Hence, there is a need for less invasive and simple techniques to replace C-OGD in this setting.

AIMS & METHODS: We aimed to compare the accuracy and acceptability of a portable, disposable, office-based, unsedated transnasal video endoscope (EG Scan™ II) with C-OGD for the detection of OV.

This was a prospective diagnostic study. Consecutive adult patients with confirmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited to participate in this study. We excluded patients with recurrent epistaxis (more than once a week); nasal obstruction; disease of the nasal cavity; history of variceal bleeding or band ligation therapy in the past 12 weeks. All subjects underwent two procedures on the same day (EG Scan followed by C-OGD), performed by two different operators blinded to the findings of the other test. Patients completed validated tolerability (10-point visual analogue scale (VAS)) and adverse events questionnaires on day 0 and day 14.

The primary outcome measure was diagnostic accuracy of EG scan (performed by one operator) against C-OGD (reference standard). In addition, interobserver agreement of the EG scan was calculated using the kappa (k) statistic, by nine blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.

RESULTS: 50 patients were recruited to the study (mean age 59 years +/-11, 70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%) completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%), p = 0.882). OV prevalence was 48.9%.

Sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95% confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI 0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI 0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis of any size OV (K = 0.45, 95%CI 0.40-0.49) and medium/large OV (K = 0.47, 95%CI 0.42-0.52).

Patients reported better experience (mean VAS+/-standard deviation (SD)) and higher preference (percentage) with EG Scan compared to C-OGD at day 0 (7.8+/-2.2 vs. 6.8+/-3.0, p = 0.058; 76.5% vs. 23.5%, p<0.001, respectively) and day 14 (7.0+/-2.3 vs. 5.5+/-3.2, p = 0.0013; 77.8% vs. 22.2%, p<0.001, respectively). There was no cowin.gov.in - Covid Vaccine Registration for 18 years old link & Process between procedure preference Easyworship 2009 keygen,serial,crack,generator,unlock sedation use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p = 0.106; day 14: OR 0.24, 95%CI 0.02-2.56, p = 0.238). 4 patients (8.5%) experienced minor self-limiting epistaxis. No serious adverse events occurred.

CONCLUSION: EG Scan was accurate for the diagnosis of any varices and clinically significant OV. Interobserver agreement was modest. More importantly, patients’ experience and preference remained significantly higher for EG Scan 14 days after procedures independent of sedation use.

Disclosure of Interest: S. Sami Financial support for research from: Intromedic Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared, R. Mansilla-Vivar: None declared, J. Fernández-Sordo': None declared, J. White: None declared, A. Khanna: None declared, M. Coletta: None declared, S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial support for research from: Intromedic Ltd, Seoul, South Korea and Olympus Keymed UK., I. N. Guha: None declared

P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE

S.H. Shin1,*, B.K. Kim1

1Department of Internal Medicine, Institue of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea, Republic Of

Contact E-mail Address:[email protected]

INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs and (2) small EVs with red sign or decompensated cirrhosis) are currently recommended for all cirrhotic patients. Recently, two new liver stiffness measurement (LSM)-based statistical equation models (PH risk score and Varices risk score) were introduced as a noninvasive, simple, accurate models for identifying presence of EVs and clinically significant portal hypertension [1].

AIMS & METHODS: We aimed to validate predictive value of the two models for detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.

Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis patients. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. LSM was measured by PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen elastography; endoscopy was used as the standard for detection of EVs. PH risk score, Varices risk score and LSPS were calculated in all cases as follows: PH risk score = -5.953 + 0.188 x LSM + 1.583 x sex (1: male; 0: female) + 26.705 x spleen diameter/platelet count ratio, Varices risk score = -4.364 + 0.538 x spleen diameter – 0.049 x platelet count – 0.044 x LSM + 0.001 x (LSM x platelet count).

RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172 (25.5%) had HEVs. The area under the receiver-operating characteristic curve (AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950 (95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other factors: Varices risk score (0.907, 95% CI 0.876-0.939, p<0.001), LSM alone (0.873, 95% CI 0.842-0.904, p<0.001). At PH risk score < 4.0, 94.6% negative predictive value (NPV) was provided (481 patients), whereas 94.3% positive predictive value (PPV) was achieved (70 patients) at PH risk score > 10.0. In the same way, at Varices risk score < -2.5, 95.6% NPV was provided (413 patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score > 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients (81.6%) and 485 patients (71.9%), respectively.

CONCLUSION: The PH risk score is a reliable, noninvasive predictive model for detection of HEVs. Furthermore, the LSPS is considered as more simply applicable model having similar predictive value. Patients with PH risk score < 4.0 may avoid endoscopy safely, whereas those with > 10.0 should be considered for appropriate prophylactic treatments.

REFERENCES

1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013; 144: 102-111.e101.

2. Kim BK, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen KH, Park JY, et al. A liver stiffness measurement-based, noninvasive prediction model for high-risk esophageal varices in B-viral liver cirrhosis. Am J Gastroenterol 2010; 105(6): 1382-1390.

Disclosure of Interest: None declared

P0044 PLALA SCORE PREDICT CIRRHOSIS PATIENT IN NONALCOHOLIC FATTY LIVER DISEASE

T. Kessoku1,*, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on behalf of JSG-NAFLD

1gastroenterology and hepatology, Yokohama city university, yokohama, Japan

Contact E-mail Address:[email protected]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic and progressive liver injury in many countries1). NAFLD includes a wide spectrum of liver diseases that range from simple steatosis, which is generally a nonprogressive condition, to nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, despite the absence of significant alcohol consumption. If NAFLD patients have liver cirrhosis, they need to be kept under surveillance for early detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in patients with NAFLD2). However, ad the number of NAFLD patients has reached 80–100 million in the United States and about 10 million NAFLD patients are estimated in Japan, it is virtually impossible to enforce in all patients.

AIMS & METHODS: To develop a mass screening system for general physicians, which can be used for predicting liver cirrhosis in NAFLD patients, using routine laboratory parameters.

A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD.

RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were selected as independent variables associated with cirrhosis in NAFLD patients by multiple logistic regression analysis. The optimal cutoff value of platelet count, serum albumin, and AST/ALT ratio was set at <15.3 104/μl (sensitivity; 81.6% specificity; 88.6%), <4.0 g/dl (sensitivity; 84.2% specificity; 84.6%), and >0.9 (sensitivity; 78.9%, specificity; 82.0%), respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AST/ALT ratio = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA ≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sensitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive predictive value).

CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

REFERENCES

1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.

2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Hepatology 1999; 30: 1356-1362.

Disclosure of Interest: None declared

P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE RETROSPECTIVE STUDY

U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1

1Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre, Denmark

Contact InPixio Photo Studio Ultimate 10.05.0 With Crack Address:[email protected]

INTRODUCTION: Carvedilol may have a greater effect on portal and systemic hypertension than propranolol although reports are conflicting 1, 2. The impact of carvedilol versus non-specific betablockers (NSBB) on mortality on patients with cirrhosis remains to be evaluated.

AIMS & METHODS: We wanted to compare the impact on mortality of carvedilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic cirrhosis from the Danish National Patient Register during the period 1995 through 2010. We used the anatomical therapeutic chemical PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen classification to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk time as the time from the first prescription of either carvedilol or NSBB until death or end of follow-up (December 31, 2010). We adjusted for gender, age, heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of diuretics. We used univariate and multivariate Cox proportional hazard models to assess the HR. Persons with missing data were excluded from the analyses (0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC, USA).

RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol and NSBB, respectively. Three patients had received both carvedilol and NSBB and were excluded. Patients from the carvedilol group were mainly classified with uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we only included patients with uncomplicated cirrhosis in our mortality analysis (80 versus 1.857 patients). Significantly fewer patients in the carvedilol group died during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square p<0.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45 (95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7). The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs. 14%) prior to cohort entry were un-evenly distributed between users of carvedilol and NSBB. We did a sub-analysis windows 10 pro license key Archives - Windows Activator we matched patients on the presence of heart disease and variceal prior to cohort entry. In this sub-analysis we compared 80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found an adjusted HR of 0.38 (95% CI 0.2-0.7).

CONCLUSION: The use of carvedilol compared with NSBB in patients with cirrhosis was associated with lower mortality in this retrospective study.

REFERENCES

1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis: a randomised study. Dig Liver Dis 2014; 46: 251-256.

2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 2002; 36: 1367-1373.

Disclosure of Interest: None declared

P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD COMPONENT USE IN CIRRHOSIS

V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2, A. Burroughs3

1Nuffield Department of Medicine, University of Oxford, 2NHS Blood and Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom

INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombotic disorder. It is a frequent indication for transfusion of blood components, both for prophylaxis and for treatment of bleeding, although indications and patterns of blood use are poorly characterised.

AIMS & METHODS: All NHS trusts with representation on the British Society of Gastroenterology membership list were invited to take part in a national audit. Data were collected prospectively on consecutive admissions with a confirmed diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/death/day 28. Specific information was requested on use of blood components, including indication, type of component and laboratory indices prior to transfusion. Standards were defined against guidelines on the use of red blood cells (RBCs), fresh frozen plasma (FFP), dvd-cloner cracked free 18.60 Crack Plus License key [2021] and cryoprecipitate.

RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years, 65% male) were collected from 85 hospitals. The predominant aetiology was alcohol (70%; 921/1313); 74% of admissions were for features of decompensation; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all admissions were transfused a blood component; in 61% (238/391) this was for treatment of bleeding and in 39% (153/391) for prophylaxis. In patients transfused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238) received RBCs, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238) cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold was >8g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis the majority (61%, 94/153) received transfusion in the absence of a planned procedure. In patients transfused for prophylaxis prior to a procedure (59/153): 19% (3/16) received FFP at an INR ≤1.5 for high risk procedures and 33% (6/18) received FFP at an INR≤2 for low risk procedures; 36% (9/25) received platelet transfusion at a platelet count>50 prior to a procedure. The most frequent procedures resulting in prophylactic transfusion were paracentesis (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboembolism was documented in 2% (29/1313) cases. Case fatality during follow up was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the most frequent cause of death.

CONCLUSION: Patients with cirrhosis are frequently transfused during hospitalisation. This audit highlights areas where greater scrutiny of blood component use is required, particularly in the group transfused for prophylaxis of bleeding. Further work is needed to improve patterns of blood use in cirrhosis to ensure patients are not exposed to unnecessary transfusion and its attendant harms.

Disclosure of Interest: None declared

P0047 SVR12 OF 99% ACHIEVED WITH A RIBAVIRIN-FREE REGIMEN OF ABT-450/R/OMBITASVIR AND DASABUVIR IN HCV GENOTYPE 1B-INFECTED PATIENTS

A. Maieron1,*, M. Puoti2, J. V. Enejosa3, P. Andreone4, Z. Ben Ari5, G. Norkrans6, M. Romero-Gomez7, W. Xie3, D.E. Cohen3, T. Podsadecki3

1Elisabeth Hospital, Linz, Austria, 2A, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. O. Ospedale Niguarda Ca Granda, Milan, Italy, 3AbbVie Inc., North Chicago, United States, 4University of Bologna, Bologna, Italy, 5The Chaim Sheba Medical Center, Tel Hashomer, Israel, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Hospital Universitario Nuestra Senora De Valme, Seville, Spain

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor (identified by AbbVie and Enanta) dosed with ritonavir (r), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Ombitasvir (formerly ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is a non-nucleoside NS5B RNA polymerase inhibitor. We report the sustained virologic response 12 weeks post-treatment (SVR12) achieved in HCV genotype 1b-infected patients after treatment with these 3 direct-acting antivirals (3D regimen) with or without ribavirin (RBV).

AIMS & METHODS: Five hundred ninety-nine treatment-naïve and prior pegIFN/RBV-experienced HCV genotype 1b-infected patients without cirrhosis were enrolled and received study drugs in the PEARL-II and PEARL-III randomized phase 3 studies. Patients were randomized 1:1 to co-formulated ABT-450/r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice daily) with or without weight-based RBV (1000 – 1200 mg daily).

RESULTS: The combined SVR12 rate from PEARL-II and PEARL-III was 99.3% in 301 patients who received 3D regimen without RBV vs. 98.7% in 298 patients who received 3D + RBV. Two patients (0.7%) receiving 3D without RBV did not achieve SVR12, both due to missing week 12 post-treatment follow-up. Four 3D + RBV patients did not achieve SVR12: 1 (0.3%) due to virologic breakthrough, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, 1 (0.3%) due to missing SVR12 data, and 2 (0.7%) due to study drug discontinuation for adverse events. SVR12 rates did not differ between 3D and 3D + RBV by baseline factors including IL28B genotype, sex, age, race, ethnicity, BMI, fibrosis stage, and HCV RNA viral load. Movavi Screen Recorder 21.4.0 Crack Full Version Download patients receiving 3D and 0.7% of patients receiving 3D PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen RBV discontinued due to adverse events.

SVR12 by baseline factors, n/N (%)3D3D + RBV
Overall299/301 (99.3)294/298 (98.7)
Treatment-naïve208/210 (99.0)209/210 (99.5)
PegIFN/RBV Treatment-experienced91/91 (100)85/88 (96.6)
IL28B non-CC genotype249/250 (99.6)240/244 (98.4)
Female160/160 (100)147/149 (98.7)
Age ≥6534/34 (100)29/29 (100)
Black race16/16 (100)13/13 (100)
BMI ≥ 30 kg/m262/64 (96.9)44/45 (97.8)
Fibrosis stage, F331/33 (93.9)33/34 (97.1)

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CONCLUSION: Irrespective of previous pegIFN/RBV treatment response and other baseline factors, HCV genotype 1b-infected patients achieved high SVR rates after 12 weeks of 3D without RBV. Overall, only 1 (3D + RBV) of 599 (0.2%) patients experienced virologic breakthrough and none experienced relapse. Both regimens were well tolerated. ABT-450/r/ombitasvir and dasabuvir without RBV achieves optimal treatment efficacy in HCV genotype 1b-infected patients without cirrhosis.

Disclosure of Interest: A. Maieron Financial support for research from: Roche, MSD, Consultancy for: MSD, Janssen Therapeutics, AbbVie, Boehringer Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, M. Puoti: None declared, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, P. Andreone Financial support for research from: Roche, Merck, Gilead, Consultancy for: Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead, MSD, BMS, Z. Ben Ari Consultancy for: MSD, Janssen, AbbVie, Boehringer Ingelheim, BMS, GSK, G. Norkrans: None declared, M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, W. Xie Shareholder of: AbbVie, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: AbbVie

P0048 ADHERENCE TO PRESCRIBED DOSES OF ABT-450/R/OMBITASVIR, DASABUVIR, AND RIBAVIRIN IN THE PHASE 3 PEARL-II, PEARL-III, AND PEARL-IV TRIALS

D. Bernstein1, R. Marinho2,*, D. Cohen3, F. Bredeek4, F. Schneider5, G. Norkrans6, M. Curescu7, M. Bennett8, M. Maevskaya9, J. Fessel10, W. Xie3, Y. Luo3, J. Enejosa3

1Hofstra North Shore- LIJ School of Medicine, Manhasset, United States, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisbon, Portugal, 3AbbVie Inc., North Chicago, 4Metropolis Medical Group, San Francisco, United States, 5Markusovszky Hospital, Szombathely, Hungary, 6Sahlgrenska University Hospital, Göteborg, Sweden, 7Life Search SRL, Timisoara, Romania, 8Medical Associates Research Group, San Diego, United States, 9First Moscow State Medical Universita n.a. I. M. Sechenov, Moscow, Russian Federation, 10Kaiser Permanente, San Francisco, United States

INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, dosed with ritonavir(r); ombitasvir(ABT-267) is an NS5A inhibitor; dasabuvir(ABT-333) is an NS5B RNA polymerase inhibitor, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. The phase 3 PEARL trials examined the efficacy and safety of all-oral, interferon-free, 12-week regimens of ABT-450/r/ombitasvir+dasabuvir(3D) with or without ribavirin(RBV) in HCV genotype(GT) 1a- and 1b-infected patients(pts). We report pt adherence to the regimens in these trials.

AIMS & METHODS: Pts were randomized to co-formulated ABT-450/r/ombitasvir(150mg/100mg/25mg QD)+dasabuvir(250mg BID) with either weight-based RBV or placebo (PBO)/no RBV. Adherence was calculated by pill counts as the percentage of capsules/tablets taken relative to the total capsules/tablets expected to be taken.

RESULTS: In each trial, mean pt adherence to every study drug was >98.5%(Table). Adherence was comparable in those who received 3D with RBV, 3D with PBO, or 3D alone. SVR12 rates were 96.6-100% in treatment-experienced and treatment-naïve HCV GT1b-infected PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen receiving 3D+/-RBV. SVR12 rates were 97.0% and 90.2%, respectively, in treatment-naïve GT1a-infected pts receiving 3D+RBV or 3D+PBO. Only 1 GT1b-infected pt had virologic failure. Pts with virologic failure had adherence rates comparable to the overall PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, but the majority was GT1a-infected and did not receive RBV. Five pts had adherence rates<80% for one or more study drugs, none of whom had virologic failure. Among 401 pts receiving 3D with RBV and 509 pts receiving 3D without RBV, 2(0.5%) and 2(0.4%), respectively, discontinued study drug due to adverse events.

PEARL-II Treatment-experienced* GT1b
PEARL-III Treatment-naïve GT1b
PEARL-IV Treatment-naïve GT1a
3D+RBV3D3D+RBV3D+PBO3D+RBV3D+PBO
Adherence, Mean % (SD)
ABT-450/r/ ombitasvir99.7 (2.3) n = 87100.0 (2.6) n = 9299.8 (1.2) n = 205100.0 (1.1) n = 20599.7 (1.9) n = 9899.7 (3.3) n = 190
dasabuvir99.0(3.2) n = 9099.2 (1.6) n = 9499.8 (1.2) n = 20599.9 (1.1) n = 20599.2 (2.0) n = 9899.1 (3.6) n = 190
RBV99.1 (6.5) n = 87NA99.6 (2.1) n = 20599.6 (2.6) n = 20398.6 (3.2) n = 9098.7 (3.6) n = 181
SVR12, % (n/N)96.6 (85/88)100 (91/91)99.5 (209/210)99.0 (207/209)97.0 (97/100)90.2 (185/205)

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Adherence data for each capsule/tablet not available for all pts.

In PEARL-II, 7 randomized patients were excluded from the intent-to-treat efficacy population because they received non-coformulated ABT-450/r/ombitasvir (N = 6) or could not be genotyped (N = 1).

CONCLUSION: Participants in these phase 3 trials had excellent adherence (>98.5%) to doses of ABT-450/r/ombitasvir, dasabuvir, and RBV. Low adherence rates, while infrequent, were not associated with virologic failure.

Disclosure of Interest: D. Bernstein Financial PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, R. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, D. Cohen Shareholder of: AbbVie, Other: AbbVie, F. Bredeek Financial support for research from: AbbVie, BMS, Gilead, Janssen, Merck, Sumagen, ViiV, Lecture fee(s) from: Merck, ViiV, Consultancy for: Merck, ViiV, F. Schneider: None declared, G. Norkrans: None declared, M. Curescu: None declared, M. Bennett Shareholder of: AbbVie, M. Maevskaya: None declared, J. Fessel: None declared, W. Xie Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie

P0049 ASSOCIATION BETWEEN TLR-3 GENE POLYMORPHISM RS3775291 AND PROGRESSION OF HEPATITIS C VIRUS INFECTION

F.-Z. Fakhir1,2,*, M. LKHIDER1

1Faculté des Sciences, Chouaib Doukkali University, El Jadida, 2Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco

Contact E-mail Address:[email protected]

INTRODUCTION: Hepatitis C virus (HCV) is a major global health problem with about 210 million people infected worldwide, and constitutes the most important cause of chronic liver disease. HCV is an enveloped positive-strand RNA virus belonging to the genus Hepacivirus of the family Flaviviridae. During the viral replication cycle, double-stranded RNA (dsRNA), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen as an intermediate, is sensed by several pattern recognition receptors (PRRs) of the innate immune system including Toll-like receptors (TLR). TLRs constitute a family of receptors playing PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen key role in innate and adaptive immune response, among them TLR3,-7 and -8, which are expressed on endosomal membrane, and have been suggested to play an important role in antiviral immune responses based on their recognition of dsRNA and single-stranded RNA (ssRNA). Single nucleotide polymorphisms (SNPs) may shift balance between pro- and anti-inflammatory cytokines, contributing to successful resistance to infection or leading to chronic inflammation and cancer. The aim of this study was to investigate the association between the TLR-3, -7 and -8 polymorphism and the outcome of HCV infection.

AIMS & METHODS: 517 patients were enrolled in the study and genotyped for the TLR3, -7 and -8 SNPs. Logistic regression was used to assess the association between the polymorphisms and the outcome of the infection.

RESULTS: A significant association between TLR-3 SNP at rs3775291 and risk of advanced liver disease was identified. The rs3775291-A/A genotype was more common in subjects with advanced liver disease than subjects with mild chronic hepatitis C (OR = 3.81; 95% CI, 2.16-6.72; p = 0.000004) and PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen difference was higher with healthy controls (OR = 5.34; 95% CI, 2.70-10.58; p = 0.000002).

CONCLUSION: Our findings indicate that a TLR-3 SNP rs3775291 is associated with progression of HCV infection to cirrhosis and hepatocellular carcinoma.

Disclosure of Interest: None declared

P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS

M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4, F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J. V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10

1Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital Germans TríasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and Southern California Research Center, Coronado, 7University of Pennsylvania, Philadelphia, 8The Queen’s Medical Center – Liver Center, Honolulu, 9AbbVie Inc., North Chicago, United States, 10University of Milan, Milan, Italy

INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition. We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) (3D regimen) with or without RBV.

AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials (PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of RBV to the safety and efficacy of the 3D regimen, were used to evaluate the incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia, jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were assessed at baseline and every 1-2 weeks per protocol.

RESULTS: Total bilirubin elevations of >3X ULN occurred in 23/401 (5.7%) 3D+RBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regimen. The majority of patients in each group (>90%) had normal total bilirubin levels at the end of treatment. Mean total bilirubin levels were significantly higher at each treatment visit in the RBV-containing treatment groups. Mean total bilirubin peaked at week 1 in both treatment groups (predominantly indirect), PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, and declined to baseline by week 2 in the RBV-free group. Events of hyperbilirubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of treatment and did not result in study drug discontinuation. One patient underwent RBV dose modification and one interrupted study drug due to hyperbilirubinaemia; both patients achieved sustained virologic response 12 weeks post-treatment. Two patients receiving 3D+RBV experienced ALT ≥3X ULN and total bilirubin ≥2X ULN, however, the timing and predominance of indirect bilirubin were not consistent with drug induced liver injury. No serious adverse events related to hyperbilirubinaemia were reported.

Bilirubin-related events, n (%)3D+RBV (N = 401)3D (N = 509)
Any bilirubin-related event21 (5.2)4 (0.8)
Hyperbilirubinaemia13 (3.2)3 (0.6)
Jaundice11 (2.7)1 (0.2)
Total bilirubin >3X ULN23 (5.7)2 (0.4)

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CONCLUSION: Low rates of hyperbilirubinaemia were observed with both 3D regiments but was less frequent in the RBV-free 3D regimens, suggesting that increases in bilirubin associated with ABT-450-containing regimens are enhanced by RBV-induced haemolysis. Bilrubin-related adverse events were infrequent with both regimens and did not affect treatment response.

Disclosure of Interest: PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen. Romero-Gomez Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, R. T. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen, R. Planas Vila Financial support for research from: Roche, MSD, BMS, Gilead, Janssen, Lecture fee(s) from: Roche, MSD, BMS, Gilead, Janssen, Boehringer Ingelheim, Consultancy for: Roche, MSD, BMS, Gilead, Janssen, D. Bernstein Financial support for research from: AbbVie, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen, Vertex, Merck, F. Rodriguez-Perez Lecture fee(s) from: BMS, Merck, Consultancy for: AbbVie, Gilead, Janssen, Merck, T. Hassanein Financial support for research from: AbbVie, Boehringer-Ingelheim, BMS, Eisai, Gilead, Janssen, Idenix, Ikaria, Mochida, Takeda, Mochida, Roche, Ocera, Sundise, Salix, Taigen, Takeda, Vertex, Lecture PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen from: BMS, Genentech, Gilead, Salix, Consultancy for: AbbVie, BMS, K. R. Reddy Financial support for research from: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Genfit, Consultancy for: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-Roche, Idenix, N. Tsai Financial support for research from: AbbVie, Janssen, Genentech-Roche, Vertex, BMS, Lecture fee(s) from: Gilead, Genentech-Roche, BMS, Vertex, Merck, Janssen, Consultancy for: AbbVie, Gilead, Janssen, S. Lovell Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, M. Colombo Financial support for research from: Merck, Roche, BMS, Gilead, Lecture fee(s) from: Tibotec, Roche, Novartis, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Bayer, BMS, Gilead Sciences, Vertex, Consultancy for: AbbVie, Merck, Roche, Novartis, Bayer, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, BMS, Gilead Sciences, Tibotec, Vertex, Janssen Cilag, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Achillion, Lundbeck, Abbott, Boehringer Ingelheim, GSK, GenSpera

P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS INDEPENDENT OF PATIENT SUBGROUPS

M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5, E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7

1Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel, Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San Diego Digestive Diseases, San Diego, 6Texas Liver Institute, PdfInspektor 2 Gold for Adobe Acrobat v1.0.022 crack serial keygen, University of Texas Health Science Center, San Antonio, 7AbbVie, North Chicago, United States

Contact E-mail Address:[email protected], [email protected]

INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta; ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a non-nucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral (3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected patients, 96.3% of treatment-naïve patients (SAPPHIRE-I trial) and 96.2% of pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV RNA <25 IU/mL at post-treatment week 12).

AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were randomized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir (150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV (1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the two trials were pooled, and SVR12 rates were calculated overall and according to race, ethnicity, and region.

RESULTS:

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