Ribavirin and interferon-alpha combination therapy vs interferon-alpha alone in the retreatment of chronic hepatitis C: a randomized clinical trial

Summary. Interferon-aL (IFN-α) induces sustained remission of chronic hepatitis C in approximately 25% of patients. In patients who are non-responders to the first course of therapy, retreatment with IFN-α is of limited efficacy. Ribavirin has also been used to treat chronic hepatitis C, but it induces only a transient response. In this study, we evaluated the efficacy of ribavirin and IFN-α combination therapy for IFN-α resistant chronic hepatitis C. Twenty-four IFN-α non-responders and 24 relapsers were randomized to receive either ribavirin (1000 mg per day) together with IFN-α (3–6 million units (MU) thrice weekly) or the same dose of IFN-α alone, for 6 months. Both at the end of treatment and 6 months later, normal transaminase levels were more common in the patients receiving combination therapy than in the group receiving IFN-α alone: 17 (70.8%) vs seven (29.2%) patients (P= 0.009) and six (25%) vs one (4.2%) patient (P= 0.034), respectively. At the end of treatment and 6 months later, serum HCV RNA was no longer detectable in eight (33.3%) and five (20.8%) patients in the combination therapy group and in six (25%) and one (4.2%) patient in the IFN-α therapy group, respectively. Three patients (12.5%) were withdrawn prematurely from combination therapy because of side-effects; ribavirin therapy was ceased or dosage reduced in six other patients (25%), again because of side-effects. In conclusion, this combination treatment was more effective than retreatment with IFN-α, alone, in inducing sustained biochemical remission of chronic hepatitis C that was resistant to a previous course of IFN-α. The combination treatment, however, was frequently associated with significant side-effects.