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Objective: The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity., Methods: Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis 3 and/or an inflammatory activity index score 8)., Results: HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8-37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31-86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03-1.7)., Conclusions: Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease.