OBJECTIVES: A randomized, placebo-controlled trial demonstrated sustained virological responses (SVR) exceeding 40% in adult patients with PNALT/CHC using peginterferon alfa-2a (40-kD) plus ribavirin (Peg/RBV) (Zeuzem. Hepatology 2003;208A). We computed prognosis, costs, and cost-effectiveness of treatment with Peg/RBV compared with no treatment in PNALT/CHC. METHODS: Sustained viral response (SVR) was 40% for 48-week treatment in genotype 1 and 72% for 24-week treatment in genotype 2/3. Disease progression was modeled based on METAVIR scores F0 to F4, followed by cirrhosis complications and death. Mean fibrosis progression rates were derived from literature reports of biopsy series in patients with PNALT. The reference is a cohort of patients with mean age 45 years with PNALT and CHC, with distribution of fibrosis at baseline equal to that found in the trial. Quality of life and costs for each health state were based on literature estimates and on European treatment patterns. Costs in 2003 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of a European National Health Service (Italian setting). RESULTS: In genotype 1, Peg/RBV compared with no treatment prolonged the time to cirrhosis by 4.8 years, increased life years (LY) by 1.4 and quality-adjusted life years (QALY) by 1 year. The incremental cost per QALY was 12,102€. In genotypes 2/3, Peg/RBV prolonged the time to cirrhosis by 8.6 years, increased LY by 2.5 and QALY by 1.8 years. The incremental cost per QALY was 1,084€. Based on the distribution in the trial of 71% genotype 1, and 28% genotype 2/3, the overall CE ratio per QALY was 7,419€. CONCLUSIONS: Treatment of adults with PNALT/CHC using Peg/RBV is projected to delay time until cirrhosis, increase life expectancy, and is cost-effective.