A randomized trial of pegylated-interferon-?2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin

Background There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. Aim To evaluate efficacy and safety of pegylated-interferon-alpha 2a plus ribavirin with or without amantadine in such patients. Methods 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha 2a 180 mu g plus ribavirin 1000-1200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha 2a 180 mu g plus ribavirin 1000-1200 mg/daily and amantadine 200 mg/daily for 12 months. Results At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and > 20% reduction of Peg-interferon were associated with the treatment failure. Conclusions The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).