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Background: Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts has been funded in Italy as the first step to diagnosing individuals who are infected but asymptomatic. The aim of this study is to evaluate the feasibility of an opportunistic HCV screening and its linkage to care. Methods: A hospital-based HCV screening was conducted as a routine test for in-patients admitted to the Evangelical Hospital Betania of Naples from January 2020 to May 2021. All consecutive in-patients were screened for the HCV antibody (HCV-Ab) at the time of their admission to the hospital, and those born prior to year 2000 were included in the study. HCV-RNA testing was required for those not previously treated and without antiviral treatment contraindications. For in-patients with an active infection, treatment started soon after hospital admission. Results: Among 12,665 inpatients consecutively screened, 510 (4%) were HCV-Ab positive. The HCV-Ab positivity rate increased with age, reaching the highest prevalence (9.49%) in those born before 1947. Among patients positive for HCV, 118 (23.1%) had been previously treated, 172 (33.9%) had been discharged before being tested for HCV-RNA, and 26 (5.1%) had not been tested for short life expectancy. Of 194 (38% of HCV-Ab+) patients who were tested for HCV-RNA, 91 (46.2%) were HCV-RNA positive. Of patients with active infection, 33 (36%) were admitted to the liver unit with signs of liver damage either not previously diagnosed or diagnosed but unlinked to care for HCV infection. Of the patients positive for HCV-RNA, 87 (95.6%) started treatment; all achieved sustained virological response. Conclusion: HCV active infection has been frequently found in patients with comorbidities admitted in the hospital in Southern Italy. To achieve HCV elimination in Italy, broader screening strategies are required. In addition to screening of the 1969–1989 birth cohort of individuals unaware of their infection status, diagnosis and linkage to care of patients with known liver damage is strictly required. Hospital screening is feasible, but prompt reflex testing for identifying HCV-active infections is necessary to increase diagnosis and subsequent linkage to care. [ABSTRACT FROM AUTHOR]