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Background: Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients. Methods: A total of 201 PegIFN-naïve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180 μg) or PegIFNα-2b (60-150 μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B ( IL28B) gene (rs8099917). Results: PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P = 0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19-15.50, and odds ratio 7.31; 95% CI 3.45-4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60 kg, women, and patients aged >60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively). Conclusions: PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype. [ABSTRACT FROM AUTHOR]