Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C

To evaluate the efficacy of a 12-month course of recombinant interferon alp ha (IFN-alpha 2b), and to assess predictive factors of successful response to IFN therapy in chronic active hepatitis C (HCV CAH), 242 patients with h istologically proven HCV CAH were assigned randomly to two groups, one trea ted with IFN-alpha 2b (3 MU three times weekly, intramuscularly), the other untreated. To determine the efficacy of IFN-alpha 2b 12 months after thera py, a second liver biopsy was carried out on 100 treated patients and 27 un treated patients. The biochemical, virological, and serological response of patients followed up for at least 50 months after treatment was also evalu ated to confirm the efficacy of IFN-alpha 2b. The genotypes of infecting HC V, anti-HCV core IgM, and HCV-RNA concentrations were also analysed and the predictors of response determined by univariate and multivariate analyses. Response was defined in terms of the normalisation of aminotransferase act ivities and the disappearance of HCV-RNA. The overall long-term response wa s 39.4%. Anti-HCV core IgM levels were significantly lower in long-term res ponders. Patients with increased levels of IgM anti HCV core (>3.8 sample/c ut-off), infected with genotype Ib were nonresponders. Liver histology impr oved significantly in patients with longterm response. Multivariate analysi s identified three independent predictors of the likelihood of long-term re sponse to IFN therapy: age younger than 40 years, basal anti-HCV core IgM l evels less than or equal to 3.8, and genotypes other than Ib. These data in dicate that the treatment with IFN-alpha 2b used in this randomised control led trial is effective in HCV CAH. Anti-HCV core IgM was the strongest pred ictor of long-term response in the present study. J. Med. Virol. 58:26-34, 1999. (C) 1999 Wiley-Liss, Inc.