Validation of the Procedure of Early Liver Transplantation in Alcoholic Hepatitis Resisting to Medical Treatment

Study Overview
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Brief Summary
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The purpose of this study is to validate a strategy of identification of patients for early liver transplantation in severe alcoholic hepatitis. In this setting, short-term survival is very low (approx. 25% at 6 months) and a pilot study has suggested (mathurin et al. N Engl J Med 2011) that liver transplantation may be an option in very carefully selected patients who did not respond to medical treatment. This selection process deserves to be confirmed in a population of greater size. We hypothesized that patients selected with this process would have a same alcohol relapse rate after liver transplantation than patients transplanted for alcoholic cirrhosis and selected using a 6-month sobriety period

Detailed Description
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Non-inferiority of alcohol relapse in early liver transplantation for severe alcoholic hepatitis as compared to patients transplanted for alcoholic cirrhosis.

Official Title
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Validation of an Accelerated Procedure of Selection in Early Liver Transplantation for Severe Alcoholic Hepatitis Not Responding to Medical Treatment QuickTransHAA.

Conditions
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Alcoholic Hepatitis, Alcoholic Cirrhosis

Intervention / Treatment
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* Procedure: Liver transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Group A): Age > 18 years Maddrey score > 32 Liver biopsy confirming the diagnosis of alcoholic hepatitis Non-response to medical treatment: Lille score ≥ 0.45 at day 7, or early worsening of liver function (MELD score > 25) despite a low Lille score (< 0.45) Hospitalization stay < 1 month Algorithm score ≥ 220/250. Inclusion Criteria (Group B): Age >18 years Diagnosis of alcoholic cirrhosis Alcoholic withdrawal of 6 months minimum before inscription on the transplant list MELD score ≥ 15 for patients with hepatocellular carcinoma responding to Milan criteria (1 node < 5 cm or 3 nodes < 3 cm) MELD score ≥ 20 preferably for patients not displaying hepatocellular carcinoma and that did not obtain an expert component No recommendation of MELD score for patients having obtained an expert component Non-inclusion Criteria (Group A and B): Bacterial or viral infection uncontrolled by medical treatment Fungal or aspergillosis uncontrolled infection Hepatocellular carcinoma or invasive cancer Positive test for HBsAg, Positive test for HIV,Positive PCR for HCV Portal thrombosis Pregnancy or breast-feeding woman

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Transplantation of alcoholic hepatitis<br>Patients of this arm will be selected for early liver transplantation for severe alcoholic hepatitis not responding to medical therapy. Selection process will be based on a specific algorithm and follow-up time will be 2 years | Procedure: Liver transplantation<br> <br> |
| Other: Transplantation for alcoholic cirrhosis<br>Patients of this arm will be selected for liver transplantation for alcoholic cirrhosis using an abstinence period of 6 months. Outcome of these patients will be compared to that of patients transplanted for severe alcoholic hepatitis. | Procedure: Liver transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of alcohol relapse in early liver transplantation for severe alcoholic hepatitis as compared to patients transplanted for alcoholic cirrhosis. | Aim is to demonstrate that alcohol relapse within the 2-year follow-up period in patients selected for early liver transplantation for severe alcoholic hepatitis is not inferior to that of patients transplanted for alcoholic cirrhosis using the 6-month sobriety period. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of the survival benefit of transplanted patients as compared to non-transplanted patients with severe alcoholic hepatitis | First secondary aim is to confirm the survival benefit of patients transplanted for severe alcoholic hepatitis as compared to patients suffering for severe alcoholic hepatitis not responding to medical treatment and not selected for early liver transplantation | 2 years | 
| Reproducibility of an algorithm of selection for candidates to liver transplantation | Second secondary aim is to evaluate the reproducibility of the algorithm for selection of candidates for liver transplantation in three centers | 2 years | 
| Incidence of alcohol relapse | Third secondary endpoint is to compare the incidence of alcohol relapse in patients selected for early transplantation for severe alcoholic hepatitis as compared to patients transplanted for alcoholic cirrhosis using the 6-month sobriety period rule | 2 years | 
| Pattern of alcohol relapse in the two groups of transplanted patients | Fourth secondary endpoint is to assess the pattern of alcohol relapse in the group of patients transplanted for severe alcoholic hepatitis to the group of patients transplanted for alcoholic cirrhosis using the 6-month sobriety rule. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic hepatitis, Liver transplantation, Alcohol relapse, Alcoholic cirrhosis