Treatment of Recurrent Hepatitis C After Liver Transplantation

Study Overview
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Brief Summary
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In France, 50% of the hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. This recurrence usually causes chronic liver disease, in 50 to 80% of the patients. The interest of a long-term treatment with ribavirin alone after transplantation has not been clearly demonstrated. The objective of our study is to evaluate the efficacy of ribavirin as a maintenance treatment after a one year interferon-α / ribavirin therapy on hepatitis C recurrence in the transplanted liver.

Detailed Description
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Several therapeutic patterns have been described for the treatment of hepatitis C post-transplantation recurrence. A combination treatment associating interferon-α and ribavirin has shown some efficacy, but this efficacy has not been assessed yet in a placebo-controlled double-blind clinical trial. In our study, all included transplanted patients will be treated during 1 year with interferon-α and ribavirin. At the end of this period, they will be randomized to receive a maintenance treatment with ribavirin or a placebo for 1 additional year. Efficacy will be assessed on virological response after 30 months of treatment.

Official Title
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Comparison of Maintenance Treatment by Ribavirin to a Placebo, After an Initial One-year Treatment With Pegylated Interferon-α2a - Ribavirin Association in Hepatitis C Viral Recurrence After Liver Transplantation

Conditions
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Liver Transplantation, Hepatitis C

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First liver transplantation or retransplantation in the month after initial transplantation Patients aged over 18 years Post-hepatitis C cirrhosis Equilibrated immunosuppressive treatment Positive PCR for hepatitis C virus Liver biopsy between 6 months and 5 years after the transplantation with a fibrosis Metavir score at least F1 Hemoglobin ≥ 10 g/dl Platelet count ≥ 50.000/mm3 Normal TSH value Serum creatinine < 200µmol/l Informed written consent Exclusion Criteria: Chronic rejection Acute rejection at inclusion Multi-visceral transplantation Renal or cardiac failure, severe sepsis Uncontrolled diabetes Positive serology for hepatitis B or HIV at inclusion EBV virus replication at inclusion Hepatocellular carcinoma at inclusion Cirrhosis with a fibrosis Metavir score F4 at inclusion Inclusion in another clinical trial less than one month ago Pregnancy Contra-indication to ribavirin or interferon History of or current psychiatric troubles Thyroid disease uncontrolled by treatment

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Ribavirin maintenance treatment | Drug: Ribavirin<br>* 18 months of oral ribavirin maintenance treatment<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 18 months oral placebo treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative viral PCR |  | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological improvement |  | 30 months | 
| Biological hepatic markers |  | 30 months | 
| Quality of life |  | 30 months | 
| Intensity, severity and delay to acute transplant rejection, histologically proven |  | 30 months | 
| Incidence of death or graft loss |  | 30 months | 
| Number of patients stopping the treatment and causes |  | 30 months | 
| Incidence of adverse events classically related to treatment |  | 30 months | 
| Incidence of adverse events possibly related to treatment |  | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Viral recurrence, Ribavirin / Interferon