Combination of interferon and ribavirin in chronic hepatitis C: Re-treatment of nonresponders to interferon

Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liv er failure, and hepatocellular carcinoma. A minority of patients have a sus tained response to antiviral therapy, and nonresponders remain at risk of d eveloping progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial cours e of therapy with IFN alone. A total of 124 patients were randomized to rec eive the combination of IFN and ribavirin for either 24 or 48 weeks and fol lowed for an additional 24 weeks after stopping therapy. Thirty-eight treat ed patients (30.6%) achieved a sustained virologic response (undetectable H CV RNA at the 24-week follow-up point). This was associated with significan t improvement in necroinflammatory activity noted on liver biopsy. Interest ingly, there was not a statistically significant difference in response rat es based on the duration of treatment; HCV genotype was the strongest predi ctor of a sustained response. Sustained responses were noted even in patien ts with poor predictive factors, including those with advanced hepatic fibr osis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. The study included 24 patients with normal serum alanine t ransaminase (ALT) values before therapy who had similar responses to those with initially elevated transaminase values. This study suggests that the c ombination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone.