Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study

The optimal therapy for patients with chronic hepatitis C who have not resp onded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-alpha 2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN. Forty consecutive patients with chronic hepatitis C, genotype 1b, who had n ot responded to IFN-alpha, were randomized to receive: (i) IFN 4.5 MU daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plu s amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN al one at the same dosage and duration (group B). After 1 month of therapy, no rmal alanine aminotransferase (ALT) values were observed in three of 21 (14 .3%) patients in group A and in three of 19 (15.8%) in group B; serum hepat itis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in grou p A and in six (31.6%) in group B. At the end of treatment, six patients (2 8.6%) in group A and three (15.8%) in group B had normal ALT levels; howeve r, HCV-RNA in serum was detectable in all of them at levels comparable to t he basal values; an ALT relapse occurred within 3 months of stopping therap y. The combination of daily IFN plus amantadine was ineffective in this set ting.