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Background: The aim was to evaluate the hepatitis C virus (HCV) cascade of care in the general population (GP) and in two high-risk populations: patients with diabetes mellitus (DM) and substance users (AS) in treatment in Reggio Emilia Province, Italy. Methods: A population-based cross-sectional study was conducted that included 534,476 residents of the Reggio Emilia Province, of whom 32,800 were DM patients and 2726 AS patients. Age-adjusted prevalence was calculated using the direct method of adjustment based on the age-specific structure of EU population. Results: The prevalence of HCV testing was 11.5%, 13.8%, and 47.8% in GP, DM, and AS patients respectively, while HCV prevalence was 6.5/1000, 12.6/1000, and 167/1000, respectively. The prevalence of HCV RNA positivity was 4.4/1000, 8.7/1000, and 114/1000 in the three populations, respectively. The rates of HCV RNA-positive individuals not linked to care were 27.9%, 27.3%, and 26% in GP, DM, and AS patients, respectively, while the rates of those cured or cleared were 70.9%, 71%, and 69.9%, respectively. The prevalence of HCV testing was higher for females of reproductive age than for males the same age: 218.4/1000 vs. 74.0/1000, respectively. While more foreigners than Italians underwent the HCV test and were HCV positive, fewer foreigners than Italians received HCV treatment and were cured. Conclusions: The low HCV testing and linkage to care rates remain an important gap in the HCV cascade of care in Northern Italy. The prevalence of cured/cleared residents remains lower among foreigners than among Italians. [ABSTRACT FROM AUTHOR]