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Objectives: The aim of this study was to evaluate retrospectively the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, epidemiological parameters, and the clinical data from the antiviral treatment of hepatitis C in a large cohort of intravenous drug users (IDUs) followed-up from 1994 until 2008., Patients and Methods: A total of 1179 former IDUs followed up either in the liver unit or in the context of a substitution program organization were included in this study. A retrospective chart review was prepared to retrieve data on the patients' demographic characteristics, the prevalence of viral hepatitis, and information on HCV treatment., Results: The prevalence of HBsAg positive was 5%. A substantial number of patients were anti-HCV positive (847/1170, 73%), 189 were lost to follow-up, 526 (80%) were HCV RNA positive and 132 (20%) had a self-limited disease. The most prevalent genotype was 3 (59.7%). Twenty-five percent of the study population received antiviral treatment against HCV infection. Patients seen in the Liver Unit were more likely to receive antiviral treatment. The sustained virological response (SVR) was 80% with patients treated with pegylated interferon and ribavirin having a significantly higher SVR rate., Conclusions: Our results show that (a) the majority of IDUs in Greece have chronic hepatitis C and the prevalent genotype is 3 (b) patients who complete therapy have SVR rates similar to those without drug-dependence, and (c) since IDUs constitute the core of the hepatitis C epidemic and the main route of HCV transmission, efforts to treat these patients should be made.