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The goal of this study was to estimate the incremental efficacy and incremental cost of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin in treatment-naïve patients with chronic hepatitis C.We used a published Markov model of disease progression in which two cohorts of patients received peginterferon α-2a plus ribavirin or peginterferon α-2b plus ribavirin for 48 (genotype 1/4) or 24 (genotype 2/3) weeks and were followed for their expected lifetimes. In the absence of a sustained virological response (SVR), the model simulated the progression from the initial health state (chronic hepatitis C) to one of five health states (compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, death) during the patient lifetime, according to specific transition probabilities derived from the literature. The sustained virological responses with peginterferon α-2a plus ribavirin and peginterferon α-2b plus ribavirin were obtained from a national clinical study in Italy. Utilities and costs for each health state were based on literature estimates and Italian treatment patterns. Costs in 2010 Euros and benefits (life years and QALYs) were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was conducted from the perspective of the Italian National Health Service.Expected life-years with peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin were 27.53 and 26.00 years (genotype 1/4) and 31.02 and 29.74 years (genotype 2/3) for the two cohorts respectively. Quality-adjusted life years for peginterferon α-2a plus ribavirin were 14.34 (genotype 1/4) and 16.13 (genotype 2/3), and 13.57 (genotype 1/4) and 15.53 (genotype 2/3) for peginterferon α-2b plus ribavirin. The expected mean cost was €25,606.78 (genotype 1/4) and €9,848.44 (genotype 2/3) with peginterferon α-2a plus ribavirin and €28,510.05 (genotype 1/4) and €12,775.09 (genotype 2/3) with peginterferon α-2b plus ribavirin.This economic evaluation suggests that peginterferon α-2a plus ribavirin is a dominant strategy versus peginterferon α-2b plus ribavirin for treatment of naïve patients with chronic hepatitis C, under the assumptions made regarding treatment effectiveness and model structure.