Retreatment with Interferon-Alpha and Ribavirin in Primary Interferon-Alpha Non-Responders with Chronic Hepatitis C.

Background/Aims: Combination therapy with interferon-α (IFN-α) plus ribavirin is more efficacious than IFN-α monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-α relapse. Only limited data are available in IFN-α non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-α-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-α-2a (3 × 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-α dose of 3 × 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-α dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-α non-responders. Higher IFN-α induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]