Interferon and ribavirin for patients with chronic hepatitis C who did notrespond to previous interferon therapy: A meta-analysis of controlled and uncontrolled trials

The efficacy of interferon (IFN) combined with ribavirin for the treatment of patients with hepatitis C who failed to respond to initial IFN therapy i s not well established. The primary goal of this study was to perform a sys tematic review of the literature evaluating the efficacy of combination the rapy in nonresponders, Studies were retrieved from MEDLINE, abstracts of sc ientific meetings, and review of the bibliographies of retrieved studies, C ontrolled trials were included in the primary analysis whereas uncontrolled trials and trials reported as abstracts were included for sensitivity anal ysis. The primary endpoints were biochemical and virologic response. A comb ined estimate of the odds ratio (OR) for each endpoint was obtained by usin g the random effects model, The number needed to treat (NNT) was calculated by taking the inverse of the pooled risk difference. Nine controlled trial s (789 patients) were identified. Six months after treatment, the overall s ustained biochemical and virologic responses to 24 weeks of combination the rapy were 15.2% and 13.2% with a common OR of 3.8 (95% confidence interval [CI] 2.2-6.7) and 4.9 (95% CI 2.1-11.2) compared with patients treated with IFN monotherapy. The pooled risk difference for the sustained virologic re sponse (SVR) to combination therapy was 7% (95% CI 2-13). The NNT was 14 (9 5% CI 8-50), suggesting that approximately 14 patients would need to be tre ated with 6 months of combination therapy for 1 patient to have a SVR. A nu mber of variables were associated with a high response rate in individual s tudies, Sensitivity analysis of preliminary trials suggest a higher respons e rate with longer duration of therapy and non-type 1 genotypes.