Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

Abstract

Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, −0.14; 95% CI: −0.27, −0.01; P = .04). A reduction in fibrosis was observed among sustained virologic responders (SMD, −0.59; 95% CI: −0.89, −0.30; P < .0001) and patients with recurrent disease (SMD, −0.34; 95% CI: −0.54, −0.14; P = .0007), whereas no significant reduction was observed among nonresponders (SMD, −0.13; 95% CI: −0.32, 0.05; P = .15). Logistic regression analysis indicated that patients with sustained virologic responses (SVRs) had an odds ratio (OR) of 1.61 (95% CI: 1.14, 2.29) for reduction in fibrosis compared with patients without SVRs, whereas obese patients (body mass index [BMI] > 30 kg/m²) had an OR of 0.56 (95% CI: 0.35, 0.90) compared with normal-weight (BMI < 25 kg/m²) and overweight patients (BMI, 25-30 kg/m²). In conclusion, in patients with chronic hepatitis C with or without cirrhosis, peginterferon alfa-2a (relative to IFN) significantly reduced fibrosis. The beneficial effects of peginterferon on liver histology are closely related to virologic response. (Hepatology 2004;39:333-342.)