Uncovering hidden HCV infections in adults over 55: reflex testing and insights for opportunistic screening in a tertiary care setting

Abstract Background Hepatitis C virus (HCV) remains a global public health concern. Despite the availability of direct-acting antivirals (DAAs), many infections remain undiagnosed—particularly in older adults excluded from national screening programs. This study aimed to assess the prevalence of unrecognized HCV infections in surgical patients over 55 years of age through an opportunistic hospital-based screening approach. Methods A single-center, retrospective observational study was conducted at “Federico II” University Hospital in Naples, Italy, from January 1 to December 31, 2023. All patients aged ≥ 18 years undergoing surgery or hospital admission were screened for anti-HCV antibodies. Reflex testing of samples with a signal-to-cut off (s/co) ratio ≥ 11 was performed with Elecsys® HCV Duo assay to confirm active infection via antigen detection. The primary endpoint was the prevalence of undiagnosed active infections in patients over 55. Secondary endpoints included distribution by age, sex, and hospital department. Results Of 33,658 patients screened, 768 (2.3%) tested positive for anti-HCV antibodies; 178 (23.2%) were antigen-positive. Active infections were most common in patients aged 55–79 (66%) and ≥ 80 (21.7%), with the highest positivity (36.5%) in those over 80. In non–high-risk departments, HCV antigen positivity reached 21.2%. No significant sex differences were observed. All antigen-positive patients received DAA treatment. Conclusions Opportunistic screening in surgical patients over 55 is effective, feasible, and cost-efficient. The high rate of undiagnosed infections in this age group supports expanding screening efforts to include older adults. These results support the national implementation of opportunistic screening programs targeting older adults to achieve HCV elimination goals. Further multicenter studies are needed to support broader implementation.