Amantadine therapy for chronic hepatitis C

Abstract

Objective: Although treatment of hepatitis C has improved, up to 50% do not respond to standard therapy with interferon regimes or cannot tolerate the treatment due to side effects. The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferon.

Design: A prospective double-blind randomized placebo-controlled trial.

Setting: Outpatient research clinic of a teaching hospital.

Patients/participants: One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes, detectable hepatitis C RNA in the blood, and abnormal liver histology by biopsy were randomized to receive treatment or placebo.

Measurements and main results: Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months. After 6 months, placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy. Amantadine therapy resulted in a significant decline in serum alanine aminotransferase compared to placebo (P =.03). Nine percent cleared the virus at the end of therapy and 6.8% had a sustained virologic response 6 months after discontinuation of amantadine, but this was not statistically significant. Side effects were minimal, and the social quality of life survey improved with 12 months of amantadine (P =.02).

Conclusions: Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon.

FIGURE 1.

ALT response to amantadine treatment. The responses of hepatic serum alanine aminotransferase (ALT) levels with amantadine 100 mg twice daily is compared to placebo. No difference in baseline ALT levels is observed between those treated with amantadine (Treatment Group A, black column) compared to those receiving placebo (Treatment Group B, gray column). Amantadine therapy significantly reduced blood ALT values at 6 months compared to placebo. Patients who received amantadine treatment only in the second 6-month interval of the study also improved compared to baseline. No difference was detected between those receiving 6 versus 12 months of therapy. Values returned to near basal values when treatment was stopped (month 18). Columns represent median ALT values and bars show the first quartile range. * Significantly different from placebo at 6 months at P= .04. ** Significantly different from baseline value at P = .008.^† Significantly different from placebo at 6 months at P= .02.^†† Significantly different from baseline value at P= .0008.