OBJECTIVE: To analyze the distribution of hepatitis C virus (HCV) genotypes among patients positive for antibody to HCV (anti-HCV) according to age, severity of liver disease, and duration of infection; to investigate the influence of HCV genotypes on response to interferon-alpha therapy; and to study HCV viremia levels in relation to genotypes and severity of liver disease. DESIGN: Cross-sectional study. SETTING: 3 university hospitals and 2 research units. PATIENTS: 3 groups of French and Italian patients with chronic HCV infection and detectable serum HCV RNA: Group 1 included 35 patients with hepatocellular carcinoma; group 2, 71 patients with cirrhosis who did not have hepatocellular carcinoma; and group 3, 114 patients with chronic active hepatitis. 106 of the patients with chronic hepatitis or cirrhosis were treated with interferon-alpha (3 MU subcutaneously 3 times/wk for > or = 6 months). MEASUREMENTS: Genotyping by polymerase chain reaction with capsid-specific primers; serum HCV RNA by branched DNA (bDNA) signal amplification. RESULTS: Hepatitis C virus genotype 1b (II) was the most prevalent genotype (61.8%). In a univariate analysis, it was associated with older age (< 40 years, 47.4%; > or = 60 years, 80.4%; P = 0.001), longer duration of disease (< or = 10 years, 40.4%; > or = 20 years, 86.7%; P = 0.005), and cirrhosis with or without hepatocellular carcinoma (78.4% compared with 53.8% for chronic hepatitis; P < 0.001). Viremia levels did not differ between patients infected with HCV type 1b (II) and those infected with other HCV genotypes. Patients with HCV type 1b (II) responded to interferon-alpha therapy significantly less than did patients with other HCV genotypes (P = 0.01). In a multivariate analysis, age and cirrhosis were independently associated with HCV genotype 1b (II). Genotype and HCV viremia level were independent predictors of response to interferon-alpha therapy. CONCLUSIONS: The prevalence of HCV genotypes in French and Italian patients has been changing; the prevalence of HCV type 1b (II) infection has progressively decreased, although it still accounts for most HCV-related cirrhosis and hepatocellular carcinoma. High HCV viremia levels and HCV genotype type 1b (II) are independent predictors for poor response to interferon-alpha therapy and should be considered in the management of patients with HCV infection.