Amantadine triple therapy for non-responder hepatitis C patients.: Clues for controversies (ANRS HC 03 BITRI)

Background/Aims: To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response. Methods: In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 mu g/kg per week and ribavirin 800-1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime. Results: Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) (P = 0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P=0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P=0.05) and week 24 (64 vs 49%; P=0.03). Fibrosis stabilized or improved in 77% of all patients. Conclusions: Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin +/- amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.