A pilot, open-labelled, phase II study using oral ribavirin in the treatment of patients with chronic active hepatitis B

Abstract

Background: Ribavirin is a synthetic purine nucleoside with demonstrated antiviral activity against several DNA and RNA viruses. Objectives: An open-labelled pilot study to evaluate the safety and effect of ribavirin in the treatment of patients with chronic active hepatitis B (CAH-B). Study design: 24 CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses for 4 weeks. Biochemical and virological parameters were monitored at regular interval during and after treatment. Results: The serum hepatitis B e antigen (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels decreased in 15 (63%) patients and became undetectable in 1 (4%) of these individuals. The mean HBV DNA decreased from 288±78 pg/ml at baseline to 219±79 pg/ml at the end of the 4 weeks of treatment ( p=0.046). Eight weeks after cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the mean HBV DNA was 46±23 pg/ml ( p<0.001 when compared to mean baseline value). Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow-up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized serum ALT at this time. The mean serum ALT decreased significantly from 416±72 IU/l at baseline to 179±35 IU/l at the end of 4 weeks of treatment ( p=0.001). Eight weeks after cessation of therapy, the mean serum ALT value was 151±32 IU/l ( p<0.001 when compared to mean baseline value) and 5 (21%) patients normalized serum ALT at this time. During ribavirin treatment, the main side effect was a decrease in the hemoglobin level which returned to the pretreatment level in each instance within 2 months after discontinuance of therapy. Conclusions: Results of this pilot study indicated that oral ribavirin was well tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA values. A randomized controlled trial is needed to fully evaluate the beneficial effects of ribavirin in CAH-B patients.