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

University Hospital, Lille284 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

284

Conditions

Alcoholic Hepatitis Alcoholic Cirrhosis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (32)

UZA

Antwerp, Edegem, Belgium

ULB, Erasme

Brussels, Belgium

Unnamed facility

Ghent, Belgium

Hospital Sart Tilman

Liège, Belgium

Univesity hospital

Amiens, France

University hospital

Angers, France

University hospital

Besançon, France

Hôpital Jean Verdier (AH-HP)

Bondy, France

University hospital

Brest, France

University hospital

Caen, France

...and 22 more locations

Outcomes

Primary Outcomes

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.

Time frame: 2 years

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 2 years