Hepatitis C, Liver Transplantation
Conditions
Keywords
Hepatitis C, Viral recurrence, Ribavirin / Interferon
Brief summary
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
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.
Interventions
DRUGRibavirin
18 months of oral ribavirin maintenance treatment
DRUGPlacebo
18 months oral placebo treatment
Sponsors
Ministry of Health, France
ANRS, Emerging Infectious Diseases
Rennes University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Negative viral PCR | 30 months |
Secondary
| Measure | Time frame |
|---|---|
| Histological improvement | 30 months |
| Biological hepatic markers | 30 months |
| Intensity, severity and delay to acute transplant rejection, histologically proven | 30 months |
| Quality of life | 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 |
| Incidence of death or graft loss | 30 months |
Countries
France
Outcome results
None listed