['Many people living with chronic viral hepatitis C (HCV) report reduced health-related quality of life. The relative contribution of behavioural, psychosocial and HCV disease factors to reduction in HCV health-related quality of life is not well understood. The objectives of the present study were to compare standardized health-related quality of life scores between Canadian HCV patients and age-matched Canadian and American norms, and to examine the relative contribution of biopsychosocial variables (ie, cigarette smoking, alcohol intake and depression) to health-related quality of life scores among Canadian HCV patients.', 'HCV RNA-positive patients were recruited during their first visit to the Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario). A questionnaire assessing health behaviours, health-related quality of life and depressed mood was completed. Data on liver studies, liver biopsy findings and HIV serostatus were also collected.', 'A total of 123 participants (71% men) ranging from 20 to 67 years of age were evaluated. All had compensated liver function. Patients reported significantly lower health-related quality of life compared with age-matched Canadian and American normative samples. In a series of hierarchical multiple regression models, depression and smoking were independently related to compromised health-related quality of life scores, even after controlling for sociodemographic variables and health behaviours.'] Do depression and cigarette smoking independently relate to reduced health-related quality of life among Canadians living with hepatitis C?