Patients with chronic hepatitis C who did not respond to previous antiviral treatment develop liver fibrosis leading to cirrhosis. Maintenance low dose pegylated interferon therapy of fibrosis is currently under investigation in large multicenter trials. The aim of our study is to assess if peginterferon alpha2b plus ribavirin is more efficient than peginterferon alpha2b alone. 454 patients will be randomized between the 2 arms and the efficacy will be assessed, after 3 years of treatment, on Metavir liver fibrosis score improvement.

Up to 45% of patients with chronic hepatitis C do not respond to pegylated interferon/ribavirin combination therapy. These patients are prone to develop liver fibrosis leading to cirrhosis and its complications. Interferon has proven to be efficient in liver fibrosis treatment even in case of virological non response. Maintenance low dose pegylated interferon therapy is currently under investigation in large multicenter trials. The aim of our study is to assess wether peginterferon alpha 2 b (0.5 µg/kg/week) plus ribavirin (800-1200 mg according to body weight) is more efficient than peginterferon alpha 2 b alone in a long term 3 years treatment of liver fibrosis. 454 patients, non responders (VHC RNA positive after 24 weeks of treatment or absence of ≥ 2 log HCV RNA drop after 12 weeks of treatment) to a previous peginterferon/ribavirin antiviral treatment will be randomized between the 2 arms, with a double-blind masking of ribavirin. The efficacy will be assessed on Metavir liver fibrosis score improvement between pre and post therapeutic liver biopsy.

Inclusion Criteria:

• Adults over 18
• With a hepatitis C virus infection (HCV RNA and anti-HCV antibodies in serum)
• Not responders to a previous antiviral treatment using the interferon plus ribavirin combination
• With a wash-out of treatment for at least 6 months
• With an active chronic hepatitis C and a Metavir fibrosis score ≥ 2
• Serum ALT levels > upper limit of the laboratory on two occasions within 6 months before inclusion
• Accepting to undergo a liver biopsy at the end of the study
• Negative pregnancy test for women
• With a social security cover
• Written informed consent

Exclusion Criteria:

• History of hepatic complications
• History of transplantation
• History of severe seizures
• History of severe psychiatric disorders
• Drug addiction within the last 12 months
• Associated condition susceptible to be responsible for liver fibrosis
• Hepatocellular carcinoma
• Cardiovascular disease unstable under treatment
• Uncontrolled diabetes
• Retinopathy
• Thyroid disease unstable under treatment
• Epilepsy and/or central nervous system functional disorders
• Autoimmune disease
• Regular alcohol consumption
• Pregnancy, breast-feeding or absence of contraception
• Haemoglobin <12 g/dl
• platelets <50000/mm3
• Neutrophils < 1200/ mm3
• Severe hepatocellular failure (prothrombin index lower than 60%)
• Renal failure (creatinine clearance lower than 50 mL/Mn)
• Associated immunosuppressive drugs, corticosteroids, antiviral drugs (other than study ones)
• Treatment with drugs likely to have an effect on fibrosis
• Anticonvulsants
• Inability to tolerate interferon