Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease

Study Overview
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Brief Summary
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The main objective of this study is the comparison of the profile of the pro-inflammatory cytokines at the patients suffering from an alcoholic hepatitis to that of two groups witnesses: patients suffering from an alcoholic cirrhosis and unhurt patients of chronic liver disease

Official Title
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Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease

Conditions
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Liver Diseases, Acute on Chronic Hepatic Failure

Intervention / Treatment
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* Other: collection of liver biopsies collection of blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: group A: patients with acute alcoholic hepatitis Active alcohol abuse defined by DSM IV and excessive alcohol consumption prior to admission (> 60 g per day for men and> 40 g per day for women) Moderate elevation of transaminases (less than 500 U / L) with a typical ASAT / ALAT ratio of 2: 1 Bilirubin> 50 mg / l Absence of autoimmune liver disease (ANA <1/80, AML <1/80, LKM1 neg, AAM neg) Absence of hepatitis B and C and HIV infection (negative anti-HIV antibodies, negative HBsAg, negative HCV PCR) Patients with other acute complications than alcoholic hepatitis may be included (eg, digestive hemorrhage, acute renal failure, infection, etc.) Because there is no validated noninvasive tool for the diagnosis of alcoholic hepatitis, histological confirmation is required in all patients (preferably by transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histological characteristics: Hepatocellular lesions (ballooning, Mallory body)/ Inflammatory infiltrate with polymorphonuclear neutrophils group B1: patients with alcoholic cirrhosis Decompensated or non-decompensated alcoholic cirrhosis, defined according to the HAS guidelines, ie by a liver biopsy or a cluster of clinico-biological arguments (www.has-sante.fr) group B2: patients free from chronic liver disease Justification of blood and liver sampling for the management of a pathology other than chronic liver disease (eg liver metastasis of digestive cancer occurring on healthy liver) Exclusion Criteria: For groups A and B1: Patients with hepatocellular carcinoma of progressive non-hepatic cancer Presence of HBsAg Presence of anti-HCV antibodies by positive PCR Presence of antibodies to HIV 1 +2 Pregnancy for group B2: Alcoholic liver disease Presence of HBsAg Presence of anti-HCV antibodies by positive PCR Presence of antibodies to HIV 1 +2 Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: acute alcoholic hepatitis<br>collection of liver biopsies collection of blood samples in patients with acute alcoholic hepatitis (group A) | Other: collection of liver biopsies collection of blood samples<br>* blood and ascites samples; extraction of explants, hepatic resection parts; hepatic parenchyma on liver biopsies<br>|
| Other: Alcoholic cirrhosis<br>collection of liver biopsies collection of blood samples in patients with alcoholic cirrhosis (group B1) | Other: collection of liver biopsies collection of blood samples<br>* blood and ascites samples; extraction of explants, hepatic resection parts; hepatic parenchyma on liver biopsies<br>|
| Other: Without chronic liver disease<br>collection of liver biopsies collection of blood samples in patients without chronic liver disease (group B2) | Other: collection of liver biopsies collection of blood samples<br>* blood and ascites samples; extraction of explants, hepatic resection parts; hepatic parenchyma on liver biopsies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the expression of proinflammatory cytokines | Proinflammatory Cytokines (TNF, IL-1, IL-6, IL-8) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the expression of genetic variants of pro-inflammatory cytokines | Identification of genetic variants of pro-inflammatory cytokines that contribute to mortality of Alcoholic Liver Disease | Baseline | 
| Cell lysis (AST, ALT, CK18 cleaved) |  | Baseline | 
| Regeneration markers (Ki-67, Fn14, CK7) |  | Baseline |