Context: Approximately 2.7 million US individuals are chronically infected with the hepatitis C virus (HCV). As public health campaigns are pursued, a growing number of treatment candidates are likely to have minimal evidence of liver damage.

Objective: To examine the clinical benefits and cost-effectiveness of newer treatments for chronic hepatitis C infection in a population of asymptomatic, HCV sero-positive but otherwise healthy individuals.

Design and setting: Cost-effectiveness analysis using a Markov model of the natural history of HCV infection and impact of treatment. We used an epidemiologic model to derive a range of natural history parameters that were empirically calibrated to provide a good fit to observed data on both prevalence of HCV seropositivity and time trends in outcomes related to HCV infection.

Patients: Cohorts of 40-year-old men and women with elevated levels of alanine aminotransferase, positive results on quantitative HCV RNA assays and serologic tests for antibody to HCV, and no histological evidence of fibrosis on liver biopsy.

Interventions: Monotherapy with standard or pegylated interferon alfa-2b; combination therapy with standard or pegylated interferon plus ribavirin.

Main outcome measures: Lifetime costs, life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.

Results: The probability of patients with chronic HCV developing cirrhosis over a 30-year period ranged from 13% to 46% for men and from 1% to 29% for women. The incremental cost-effectiveness of combination therapy with pegylated interferon for men ranged from 26 000 dollars to 64 000 dollars per QALY for genotype 1 and from 10 000 dollars to 28 000 dollars per QALY for other genotypes; and for women ranged from 32 000 dollars to 90 000 dollars for genotype 1 and from 12 000 dollars to 42 000 dollars for other genotypes. Because the benefits of treatment were realized largely in the form of improvements in health-related quality of life, rather than prolonged survivorship, cost-effectiveness ratios expressed as dollars per year of life were substantially higher. Results were most sensitive to assumptions about the gains and decrements in health-related quality of life associated with treatment.

Conclusions: While newer treatment options for hepatitis C appear to be reasonably cost-effective on average, these results vary widely across different patient subgroups and depend critically on quality-of-life assumptions. As the pool of persons eligible for treatment for HCV infection expands to the more general population, it will be imperative for patients and their physicians to consider these assumptions in making individual-level treatment decisions.