Efficacy of high-dose interferon in combination with ribavirin in patientswith chronic hepatitis C resistant to interferon alone

OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its u tility in patients who have not responded to prior interferon therapy is no t clear. Furthermore, the effect of using an increased dose of interferon i n combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavir in on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive eithe r 3 or 5 MU of interferon alpha -2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA l evels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68 yr), and 110 ( 71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21(14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha -2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virol ogical response to the 12-month course of treatment. Overall, 11 of 81 pati ents (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of in terferon maintained an undetectable HCV RNA level after cessation of therap y. The difference in sustained response rates between the two interferon do sage groups did not reach statistical significance (p = 0.09). However, amo ng the nonresponder patients alone, there was an increased sustained respon se in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued the rapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 pati ents (21.9%) in the 5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined interferon alpha -2 b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treate d patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the pri or nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable. (Am J Gastroenterol 2001;96: 1143-1149. (C) 2001 by Am. Coll. o f Gastroenterology).