Comprehensive Evaluation of the Elecsys® HCV Duo Immunoassay for Active Hepatitis C Detection: Insights from the DEPCDUO Study

Early diagnosis of Hepatitis C virus (HCV) infection is a cornerstone of elimination strategies. Fourth-generation antigen/antibody combination assays, such as Elecsys® HCV Duo, promise to bridge the diagnostic gap left by antibody-only testing. In this real-world study, we assessed Elecsys® HCV Duo performance using seroconversion panels and routine clinical samples, focusing on sensitivity, specificity, and positive predictive value (PPV) for active HCV detection, including challenging scenarios with low viral loads and HIV co-infections. The assay shortened the serological window by up to 203 days. When both antigen and antibody were detected, PPV reached 100%, enabling confident diagnosis without immediate RNA confirmation. The antigen component alone achieved a PPV of 97.6%, even in a low-prevalence setting (0.33%), better than previously reported assays. However, sensitivity for low viral loads (≤ 5 log IU/mL) was limited, with 95.5% of such cases missed. Elecsys® HCV Duo offers a powerful tool for earlier detection and streamlined care, particularly in high-risk and resource-limited contexts. Yet, confirmatory RNA testing remains essential for low viral load cases. Broader validation is needed to confirm its utility in diverse populations, reinfection surveillance, and cost-effective screening strategies.