We conducted a three-arm, randomized trial in 96 patients with
chronic hepatitis C who did not respond to
interferon alfa to compare treatments. Group 1 (33 patients) received
ribavirin alone (1,000 mg/daily for 6 months) followed by
interferon alfa n-3 alone (3 MU thrice weekly for 6 months); group 2 (33 patients) received
ribavirin plus
interferon alfa n-3 for 6 months at the above doses; and group 3 (30 patients) received
interferon alfa n-3 alone (3 MU thrice weekly for 6 months). At the end of treatment, 3 patients (10%) in group 1, 13 (41%) in group 2, and 5 (17%) in group 3 had normal
alanine transaminase (ALT) levels (group 2 vs. groups 1 and 3, P = .008). After 6 months of follow-up, only 4 patients (12.5%) in group 2 still had normal ALT values (P = .03). At the end of
therapy, hepatitis C virus (HCV)
RNA was no longer detectable by polymerase chain reaction in 4 (13%), 9 (27%), and 2 (7%) patients, respectively, in groups 1, 2, and 3 (P = NS). Six months posttherapy, only 5 (15%) patients in group 2 were still HCV
RNA negative (P = .02). At the time of follow-up liver biopsy, performed 6 months after the end of treatment, a significant improvement of the necroinflammatory scores was observed among group 2 patients (P = .01) but not in the other two groups. Side effects reflected the profile of each
drug as monotherapy; mild
hemolytic anemia was the most frequent side effect caused by
ribavirin. In conclusion, concomitant administration of
ribavirin and
interferon alfa n-3 was significantly superior to the sequential schedule or
interferon alfa n-3 monotherapy in inducing a sustained response in patients with
chronic hepatitis C who had not responded to
interferon alone. However, combination
therapy at the dose and duration adopted in this study is capable of modifying the natural course of the disease in only a minority of these patients.