Assessment of nutrition in liver cirrhosis

Category 8: Nutrition, metabolism, alcoholic liver disease, pharmacology

I

696

THERAPEUTIC EXEICISE

EFFECTS

IS OF BENEFIT

NON-ALCOHOLIC N. Sasaki’,

‘Nag&a

Yanagawa;

DIET AND

TO PATIENTS WITH

STEATOHEPATITIS

T. Ueno2, Y. Morita’,

Hospital,

OF RESTRICTED

S. Yoshiok’,

2Kurume

(NASH)

E. Nag&a’,

M. Sata2.

University School Of Medicine,

Kurume, Japan

Aim: Non-alcoholic steatohepatitis (NASH) is commonly induced by obesity, diabetes and hyperlipidemia. Therefore, restricted diet and exercise is very important in its therapy. In the present study, we examined the effects of restricted diet and exercise for patients with NASH and compared therapeutic effects between the patients with NASH and those of the fatty liver alone. Methods: In this study, 17 cases (12 obese patients [Body mass index (BMI) >25kg/m2] with NASH: [NASH group] and 5 obese patients with fatty liver alone: [FL group] followed a program of restricted diet (ideal weight x 25-30 Cal/day, fat 30%, protein 20% and carbohydrates 50%) and exercise (walking or jogging for 40 minutes per day) for a trial period of 3 to 6 months after informed consent. Diagnosis was confirmed histologically. BMI, blood biochemistry, ultrasound assessment and liver biopsy specimens were compared in all patients before and after treatment. Results: Before treatment; In histological findings of liver biopsy specimens, hepatocyte ballooning, intralobular cell infiltration, Mallory’s bodies in the NASH group were remarkable compared with those in the FL group. There were no significant differences in age, BMI, blood biochemical data such as AST, ALT, total cholesterol and triglyceride between the NASH group and FL group. After treatment; In the NASH group as well as FL group, BMI, biochemical data containing AST and ALT, and histological findings such as steatosis, lobular inflammation and lipogranuloma improved significantly. However, there was no significant difference on the degree of fibrosis in periportal, intralobular and perivenular areas before and after treatment in the two groups. Conclusions: A combination therapy of restricted diet and exercise is one of very important therapies for the patients with NASH. This therapy brings the improvement of not only symptoms and blood chemistry but also histrogical findings such as steatosis, hepatocyte ballooning and intralobular inflammation. In addition, the improvement of hepatic fibrosis in the NASH group as well as the FL group seems to require more time.

I

697

EARLY OSTEOPENIA PREVALENCE

IN CHRONIC

AND ASSOCIATED

HEPATITIS C: FACTORS

C. Silvain’, I. Ingrand2, M. Flahault3, F. Debiais4, M.P. Bounaud’, L. Becq-Giraudon6, C. Millet7, M. Beauchant. ‘Hepatology Unit University Hospital Poitiers; 2Faculty Of Medecine, Unit, Poitiers; 4Rhumatology 6Hepatology

Unit, Poitiers; ‘Nuclear

Unit, Poitiers; 7Nuclear Medecine,

Poitiers; ‘Hepatology Medecine,

Poitiers;

Poitiers; ‘Hepatology

Unit, Poitiers, France

Chronic liver diseases with or without cirrhosis have been shown to be associated with osteopenia and osteoporosis. However, prevalence and mechanisms are not well known in chronic hepatitis C without cirrhosis. The aim of this prospective study was to evaluate the prevalence and factors associated with their outcome in order to elucidate the mechanisms involved in their pathogenesis. Patients with non cirrhotic chronic hepatitis C (HCV, n=45), with liver biopsy (METAVIR score) were age- and sexmatched with patients with non cirrhotic alcoholic chronic liver disease (CAH; n=36) and normal controls (C; n=37). Bone mineral density (BMD g/cm2 and T score) was measured using dual-energy X-ray absorptiometry biphotonique at lombar and hip sites (neck, trochanteric, total). Biochemical markers of bone turnover and osteoporosis were measured. Serum levels of TNI-alpha, II-l, II-6 were measured by ELISA and IGF-1 by RIA (gn/lm/gm). R SULTS: T score were as followed: a) lombar: HCV: -1, 018b; CAH: -1, 178a;C: -0, 506;b) neck: HCV: -1, 404a; CAH: -1, 788a;C: -0,693; trochanteric: HCV: -0, 608b; CAH: -0, 897b;C: -0,333. a p
201

controls whatever the considered bone site. In HCV patients, biochemical markers of bone turnover and osteoporosis were not significantly modified compared with controls. In HCV patients a positive correlation was noted between BMD and 250Hcalciferol and a negative one between BMD and BAl? IGF-1 levels were significantly lower in HCV (HCV: 114, 65; CAH: 103, 24; controls: 156, 67) and TNF-alpha levels significantly elevated in HCV (HCV: 107, 71; CAH: 19, 43; controls: 16, 65) and not correlated with any biochemical markers of bone turnover. In HCV patients without cirrhosis, a significant diminution of bone mass is present. No biochemical markers of bone turnover and osteoporosis predictive of this early osteopenia were found. Apart from smoking no aggravating factor was evidenced. Pathogenesis is complex but hepatitis C virus per se seems to have an important role.

I

698

ALCOHOL

DEHYDROGENASE

ASSOCIATED

3~1 GENOTYPE

WITH HEPATOCELLULAR

ALCOHOL-INDUCED

IS

CARCINOMA

IN

LIVER CIRRHOSIS

F. Stickel’, M. Benesova2, H.K. Seitz2, I. Zuber-Jerger3, C. Hellerbrand4, M. Frieser’, W.H. Caselmann’, H.E. Blum3, E.G. Hahn’, D. Schuppan’. ‘Department Erlangen,

Of Medicine

I, University Of Erlangen-Nuremberg,

Get-many; 2Laboratory

Of Alcohol Research,

Salem Medical

Centec Heidelberg,

Get-many; ‘Department

Of Medicine

II, University Of

Freiburg,

Get-many; 4Department

Of Medicine

I, University Of

Freiburg,

Regensburg,

Regensburg,

Get-many; ‘Department

Of Medicine,

University

Of Bonn, Bonn, Get-many

Chronic ethanol consumption may lead to liver cirrhosis which is associated with an increased risk for hepatocellular carcinoma (HCC). Among other factors, increased acetaldehyde (AA) production via alcohol dehydrogenase (ADH) has been suggested as a pathogenic mechanism. The isoenzyme ADH3 reveals genetic polymorphism and the allel ADH3*1 encodes for an enzyme with a high capacity to generate AA. Lately, an association was shown between the ADH3*1 allel and oropharyngeal cancer in alcoholics. ADH3 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in patients with alcohol-associated HCC (A-HCC, n=70), patients with HCC due to viral hepatitis B and C (V-HCC, n=38), alcoholic cirrhotics without HCC (AC, n=39), cirrhosis caused by viral hepatitis (VC, n=26), and in healthy controls (C, n=48). Genotypes were A-HCC: ADH3*1/1, n=28; ADH3*1/2, n=32; ADH3*2/2, n=lO; V-HCC: ADH3*1/1, n=lO; ADH3*1/2, n=12; ADH3*2/2, n=16; AC: ADH3*1/1, n=8; ADH3*1/2, n=23; ADH3*2/2, n=8; VC: ADH3*1/1, n=3; ADH3*1/2, n=19; ADH3*2/2, n=4; controls: ADH3*1/1, n=ll; ADH3*1/2, n=26; ADH3*2/2, n=ll. The allele frequencies of the ADH3*1 in A-HCC, V-HCC, AC, VC, and C were 62.9%, 42.1%, 50%, 48.1% and 50%, respectively, and the rates homozygosity were 40.0%, 26.3%, 20.5%, 11.5% and 22.9%, respectively. Allele frequency and rate of homozygosity of ADH3*1 was significantly higher in patients with A-HCC compared to all other groups (p
I

699

ASSESSMENT

OF NUTRITION

IN LIVER CIRRHOSIS

G. Tasan, N. Tozun, V. Tahan

F.Y. Enc, A. Giral, N. Imeryuz, E. Avsar, C. Kalayci. DepartmentOfc’astroenterology, Marmara University School Of Medicine,

Istanbul, Turkey

Objectives: Restitution of mortality and morbidity in effect of NS on total body fat (BF) and bone mineral ray absorptimetry (DEXA) LC.

altered nutritional status (NS) may improve liver cirrhosis (LC). We aimed to evaluate the mass (TBM), lean body mass (LBM), body content (BMC) measured by dual energy Xand other anthropometric parameters (AP) in

202 Methods: 22 Child-C cirrhotics (F/M: 9/13; mean age .54&l 1.0 years), and 18 healthy-subjects (F/M: 9/9; mean age .54.2&8.7 years) were studied. AP including body mass index (BMI), triceps skin-fold thickness (TSF), midarm circumference (MAC), mid-arm muscle circumference (MAMC) and handgrip-dynamometry were measured. TBM, LBM and BF were assessed by DEXA. Dietary intake was assessed by a weekly query form. Results: AP results of cirrhotics were significantly lower than healthysubjects (Table 1). Daily calorie, protein and fat intakes were significantly lower in LC (p
TSF cm

parameters

MAC

cm

MAMC

of Child C cirrhotic cm

patients, and control DEXA-tissue

BMD

1

12.4&6.X*

23.4&3.87

23.0&3.71

0.25&0.2t

64702&1113Ot

2342&3

22.4&7.1

29.7&4.9

29.0&4.X

0.5*0.1

73436&8783

3022&4

Child C Cirrhosis

tp
(~22);

2

Healthy Control

(1~18);

BMD:

700

AlTENUATES

Bone mineral density;

LIVER INFLAMMATION

RAT MODEL OF NON-ALCOHOLIC

IN A

STEATOHEPATITIS

V. Tahan’, F. Eren2, D. Yavuz3, E. Emekli2, M. Yukse14, Z. Goren’, C. Celike16, G. Haklar4, E. Avsar’, N. Tozun’. ‘Department Of Gastroenterology, Marmara University School Of Medicine, Istanbul, Turkey; 21nstitute Of Gastroenterology, Marmara University, Istanbul, Turkey; ‘Department Of Endocrinology, Marmara University School Of Medicine, Istanbul, Turkey; 4Department Of Biochemistry, Marmara University School Of Medicine, Istanbul, Turkey; ‘Department Of Pharmacology, Marmara University School Of Medicine, Istanbul, Turkey; 6Department Of Pathology, Marmara University School Of Medicine, Istanbul, Turkey Objectives: Insulin resistance (IR) and increased reactive oxygen species (ROS) were reported in the pathogenesis of non-alcoholic steatohepatitis (NASH).The aim of this study was to assess whether rosiglitazone, an oral antidiabetic agent could correct IR and improve steatosis in a rat model of NASH. Material/Methods: 36 male Wistar-rats were divided into 4 groupsGroup1 (10 rats) and group-2 (10 rats) received methionine and choline-deficient diet (MCDD);group-3: (8 rats) and group-4: (8 rats) received control diet (MCDD plus choline and methionine), group-l and group-3 also received rosiglitazone maleat (10 micromol/bw/d) for 4 weeks. Liver pathology (steatosis, inflammation and fibrosis), liver tissue-ROS (Luminol and Lucigenin), serum ALT, AST, alkaline phosphatase (ALP), total cholesterol

Abstract

Group-l

700 -Table

n=lO

1. Biochemical

SUBCUTANEOUS

INTERLEUKIN-10

CORTICOSTEROIDS ALCOHOLIC

PLUS

IN THE TREATMENT

HEPATITIS.

RESULTS

OF SEVERE

OF A PILOT STUDY

C. Delarche2, M. Cohard4, A. LeBeaut4, l? Cluzel’, B. Bernard’, M.A. Gougerot-Pocidalo2, T. Poynard’,3. ‘Hepatology Department, Pitie Salpettiere Hospital, 47 Bd De L’hopital 75651, Paris Cedex 13, France; 21mmunology Department And INSERM U479, Bichat Hospital, 46 Rue Hem-i Huchard 75018, Paris, France; ’URA CNRS 1484,4 Avenue De L’observatoire 75006, Paris, France; 4Schering Plough Research Institute, Kenilworth, USA; ‘Vascular Radiology Department, Pitie Salpettiere Hospital, Paris, France

*p
ROSIGLITAZONE

701

J. Taieb’,2,3, S. Chollet Martin2,

Conclusions: The positive correlation between dietary intake and anthropometric and DEXA parameters in LC suggests that diet plays an important role in this group. Diminished appetite and inappropriate dietary restrictions contribute to malnutrition in LC. Studies in large groups are needed to show the correlation of malnutrition and complications of LC.

I

I

group

Handgrip-bar

2 1

and triglyceride levels were studied. Glucose metabolism was determined by-OGTT. Results: After 4 weeks of induction a marked and similar degree of steatosis was observed in both group-l and-2 rats, fed MCDD, while group-l resulted in lesser liver inflammation than group-2 (p=O.O32) and lower levels of serum ALT (p=O.O16) and ALP (p=O.O28).Group-3 and-4 showed no histological changes. The biochemical findings of groups were summarized in Table 1 (see below). Conclusions: Short-term use of rosiglitazone significantly attenuated liver inflammation, ALT and ALP elevations in MCDD rat model of NASH, but had no effect on steatosis.

Interleukin 10 (IL-lo) is a cytokine with immunosuppressive and antiinflammatory activities. Patients with severe alcoholic hepatitis (AH) have a major inflammatory reaction and low plasma IL-10 levels associated with a poor monocytes IL-10 synthesis capacity. The present pilot study was designed to evaluate the safety and tolerance of IL-10 therapy in severe AH. The impact of II-10 on specific biological and immunological parameters related to AH pathophysiology was also evaluated. Thirty two patients were studied: 8 patients with severe AH treated with corticosteroids for 28 days and recombinant human IL-10 (8mg/kg/d) administered once daily subcutaneously during the same period, and 24 controls treated with corticosteroids alone (matched for age, gender, Child-Pugh score and serum creatinine levels). As measures of blood neutrophil (PMN) function, L-selectin and b2-integrin expression, H202 production, and K-8 and TNFa synthesis capacity together with changes in plasma levels of K-8 and TNFa during therapy, were measured in all IL-10 treated patients and in eight controls. Treatment was generally safe and well tolerated. Two II-10 treated patients developed severe thrombocytopenia, but no bleeding was observed, and the platelet counts returned to normal after treatment discontinuation or dosage reduction. No differences between groups were noted in the decrease of Maddrey’s discriminant function during therapy or survival at the end of treatment. Before therapy, plasma levels of K-8 and TNFa were high and blood PMN were activated. At the end of the treatment period, no significant changes in PMN functions were observed for adhesion molecule expression and H202 production in K-10 treated patients. PMN-derived II-8 and TNFa as well as changes in plasma levels of TNFa and IL-8 were not different between the two groups. In conclusion, these preliminary results suggest that subcutaneous K-10 associated with corticosteroids is safe, but of limited biological or clinical efficacy in patients with severe AH.

findings

Luminol

Lucigenin

AST

ALT

ALP

Total-C

TG

nulmg tissue

nulmg tissue

UA

UA

UA

mgldl

mgldl

3.9X&2.54’)

11.73*5.032)

229&X93)

10x*2x4)

7x1*3515)

2X&136)

49*

OGTT (AUC)

147’

14x*358)

Group-2

n=lO

3.43&1.61

9.36&3.96

277&79

173&X2

1338&551

39*11

52&12

165&57

Group-3

n=X

0.76&0.49

5.X0&1.16

17 1*4x

47*10

704*

199

66&19

4x*x

40*55

Group-4

n=X

0.57&0.20

5.10*1.34

158&29

43*7

549*

15 1

63&5

77&38

61&65

ALP:

Alkaline

Phosphatase,

group 2 and p
Total-C:

total-cholesterol,

vs groups 3 and 4; 5)p<0.02X

TG: hichlyceride;

vs group 2; 6)p<0.017

‘)p
vs groups 3 and 4; ‘)p
vs group 2 and p
vs groups 3 and 4; 3)p<0.001

vs groups 3 and4;

‘)p
vs groups

vs group 4; ‘)p
3 and 4; 4)p<0.016

vs group 3;

vs