Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine

Abstract

There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.