This project is aimed at developing practical, safe and effective means of preventing the progression of liver disease in patients with chronic hepatitis C virus (HCV) infection. Approximately 800 patients with chronic hepatitis C who have failed to respond to therapy with alpha interferon (with or without ribavirin) and who have significant fibrosis on liver biopsy will be enrolled in a study of the efficacy and safety of a continuous long-term antiviral therapy (for as long as four years). The objective of the Trial is to evaluate whether continuous therapy with long-term antiviral therapy can slow the progression of liver disease, preventing cirrhosis or preventing worsening of cirrhosis, decompensation, development of hepatocellular carcinoma (HCC) and death from liver disease. The Trial will also evaluate the natural history of hepatitis C and the factors that predict or correlate with disease progression. The major focus will be to evaluate whether antiviral therapy, despite not leading to eradication of HCV, can suppress hepatocellular injury, necrosis and fibrosis. Patients with chronic hepatitis C who have previously been treated with alpha interferon without a sustained virological and biochemical response will be eligible to enter the Trial.