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Hepatitis C in a Mobile Low-Threshold Methadone Program. INTRODUCTION: Data on the epidemiology of hepatitis C among individuals who use drugs in low-threshold settings are lacking, although crucial to assess the burden of disease and aid in the design of treatment strategies. OBJECTIVE: The aim of this study was to characterize the epidemiology and disease related to hepatitis C in a population attending a low-threshold methadone program. MATERIALS AND METHODS: A cross-sectional study in the population attending the Mobile Low-Threshold Methadone Program in Lisbon, Portugal, was carried out. The survey included assessment of risk factors for infection with hepatitis C virus (HCV) and liver disease, HCV serology and RNA detection, HCV genotyping, and liver disease staging. RESULTS: A total of 825 participants were enrolled, 81.3% men, mean age 44.5 years. Injecting drug use (IDU) was reported by 58.4% - among these, 28.2% were people who inject drugs. Excessive drinking and HIV coinfection were reported by 33.4 and 15.9%, respectively. Among participants with active infection, 16.9% were followed up in hospital consultation. The overall seroprevalence for HCV was 67.6% (94.2% in IDU, 30.0% in non-IDU, 97.1% in people who inject drugs, and 75.6% in excessive drinkers). Among seropositives for HCV, active infection was present in 68.4%. Among individuals with active infection, the most common genotypes were 1a (45.3%) and 3a (28.7%), whereas 30% had severe liver fibrosis or cirrhosis. Age 45 years or older, HCV genotype 3, and coinfection with HIV were significant predictors of cirrhosis. CONCLUSION: This population has a high burden of hepatitis C and several characteristics that favor dissemination of infection. Healthcare strategies are urgently needed to address hepatitis C in this setting.