Efficacy of prolonged interferon therapy for patients with chronic hepatitis C with HCV-genotype 1b and high virus load

Background: In patients with hepatitis C virus (HCV)-genotype 1b and a high virus load, of more than 1 Meq/ml by the DNA probe assay, the clearance of HCV-RNA was achieved in only 10% with a 6-month interferon (IFN) course. We therefore assessed the efficacy of prolonged IFN therapy in patients with HCV-genotype 1b and a high virus load. Methods: A total of 51 patients with HCV genotype 1b who were given 6 million units (MU) of natural IFN-α daily for 8 weeks followed by three-times-weekly treatment with natural IFN-α for 16 weeks, were enrolled in this trial. These 51 patients were randomly assigned to one of two schedule groups at the time of termination of the first IFN therapy. The 48-week-group patients (n = 25) were given 6 MU of natural IFN-α by intramuscular injection three times weekly for 24 weeks, beginning within a week after the termination of the first IFN therapy. The 72-week-group patients (n = 26) were given 6 MU of IFN-α by intramuscular injection three times a week for 48 weeks, beginning within a week after the termination of the first IFN therapy. The therapeutic efficacy was evaluated 24 and 30 months after the initiation of the first IFN treatment. A virological response (VR) to IFN therapy was defined as the normalization of serum alanime amino transferase (ALT) level (ALT ≲ 50 IU) and HCV-RNA negativity at the two time points. Biochemical response (BR) was defined as the normalization of serum ALT, but positivity for HCV-RNA, assessed by commercial Amplicor HCV qualitative assays, at the two time points. Results: The efficacy of IFN treatment was assessed in relation to the IFN administration schedule by intention-to-treat (ITT) analysis and per-protocol analysis. With respect to the IFN regimen, VR occurred in 16.6% (4/24) of the patients in the 48-week-group with additional IFN and in 20% (5/25) in the 72-week-group with additional IFN by ITT analysis. The BR rate was 33.3% (8/24) in the 48-week group and 48% (12/25) in the 72-week group. Conclusions: We found that prolonged IFN therapy could be a worthwhile treatment strategy for patients with HCV genotype 1b and a high serum virus load. Received: March 15, 2002 / Accepted: July 26, 2002 Reprint requests to: Y. Arase Editorial on page 204