OBJECTIVES: Infection with hepatitis C virus (HCV), which affects approximately 3% of the global population, may be associated with extra-hepatic manifestations such as cardiovascular diseases, lymphoproliferative diseases, diabetes and renal impairment, which contribute to the burden of HCV and may impact patient care and prognosis. Therefore, the objective of this study was to describe the prevalence of multiple comorbidities among patients ± HCV in a large health maintenance organization (HMO). METHODS: The study was performed using the computerized databases of Maccabi Healthcare Services (MHS), a 2-million-member HMO representing a quarter of the population in Israel. Patients enrolled in MHS in 2012 with a record of HCV infection were identified by cross-linking physician diagnoses, laboratory tests (e.g. detection of HCV antibodies and RNA) and dispensed prescriptions for HCV treatment.  A matched group of patients with no indication of HCV infection was selected by individual matching (1:4) on sex, age, origin, and district of residence. Comorbidities were identified using the MHS automated patient registries, the National Cancer Registry, and International Classification of Disease, 9^thedition, diagnoses. Prevalence of comorbidities was estimated for each group (i.e. patients ± HCV). RESULTS: The mean age of HCV patients was 49 years (n=10,521; 43% female). Preliminary results indicate that compared to matched HCV-negative patients (n=42,084), HCV patients had a higher prevalence of multiple comorbidities, including diabetes, stroke, atrial fibrillation, hypertension and chronic kidney disease. HCV patients were also more likely to have a history of smoking and substance abuse. CONCLUSIONS: The study results indicate that multiple comorbidities are prevalent among HCV patients. As we move into a new era of HCV treatment, it is important to monitor extra-hepatic manifestations in real-world settings and to assess the potential implications of multiple comorbidities on patient care and prognosis.