PURPOSE: Our study aimed to identify factors associated with the occurrence of severe liver disease in hepatitis C virus (HCV) positive patients at first referral to hepatology reference centers in France in 2001. METHODS: Patients reported through the national hospital-based hepatitis C surveillance system in 2001 were included. The definition of severe liver disease was based on clinical, biological, and morphological evaluation; cirrhosis (+/- complication) and primary liver cancer were classified as severe liver disease. Patient characteristics were compared for those with and without severe liver disease. RESULTS: Of the 3404 newly referred patients in the 26 participating centers, 391 (11.5%) had severe liver disease. Male gender (adjusted odds ratios [aOR]=1.4; 95% confidence interval [CI], 1.0-1.9), age over 39 years at referral (aOR=3.8; 95% CI, 2.7-5.3), past excessive alcohol consumption (aOR=2.6; 95% CI, 1.9-3.5), and HIV seropositivity (aOR=1.9; 95% CI, 1.1-3.3) were each independently associated with an increased risk of severe liver disease. In the subgroup of patients with known age at time of HCV exposure, age over 39 years at time of exposure (aOR=1.6; 95% CI, 1.1-2.4), duration of HCV infection over 15 years (aOR=2.6; 95% CI, 1.8-3.7), known HBs antigen positivity (aOR=2.4; 95% CI, 1.1-5.2), and past excessive alcohol consumption (aOR=2.7; 95% CI, 1.8-3.9) were each associated with increased risk of severe liver disease. CONCLUSIONS: Our findings underscore the important role of past excessive alcohol consumption on the development of severe liver disease for HCV patients.