Multicenter evaluation of the Elecsys® HCV Duo assay performance, diagnostic agreement, and utility in active HCV infection triage

Abstract Background To evaluate the performance and diagnostic agreement of the novel Elecsys ® HCV Duo immunoassay with standard comparator workflows, and to assess its dual antibody and antigen detection capabilities for triaging active HCV infection. Methods Serum samples were collected from patients with confirmed HCV infection or those at high risk of HCV infection at three hospitals in China. Clinical and demographic information including comorbidities, sample collection dates, and HCV RNA results were collected from the medical records. The performance of the Elecsys ® HCV Duo Ab and Ag modules was evaluated against both the two-assay algorithm combining Elecsys ® Anti-HCV II and ARCHITECT HCV Ag, and the individual assays, using serum samples and seroconversion panels. Results HCV Duo demonstrated robust performance across 923 samples, showing high agreement with the two-assay algorithm of Anti-HCV II and ARCHITECT HCV Ag (OPA: 96.97%). Among the 215 Anti-HCV-reactive samples with available HCV RNA results, HCV Duo showed high concordance with Anti-HCV II, achieving 100% agreement (132/132) in the RNA-positive subgroup and 98.8% agreement (82/83) in the RNA-negative subgroup. The HCV Duo Ag module showed comparable sensitivity to ARCHITECT HCV Ag (55.3% vs. 56.8%) in Ab+/RNA+ samples and the detection sensitivity increased with elevated RNA levels. Notably, the HCV Duo identified active infections in 34% of Ab+ cases through concurrent Ag+ detection. Moreover, HCV Duo demonstrated consistent detection performance in samples from patients with other viral infections, immunocompromised states, or interfering factors. In the analysis of seroconversion panels, both antigen assays substantially shortened the diagnostic window compared to traditional antibody testing, with HCV Duo reducing it from 28.67 days to 1.58 days after HCV RNA detection, and the standalone ARCHITECT HCV Ag assay achieving slightly earlier detection with a mean delay of 0.42 days. Conclusion The Elecsys ® HCV Duo assay showed good agreement with the comparator workflow. Its capacity to shorten the diagnostic window may effectively support early HCV screening or triage. However, HCV RNA testing remains necessary when active infection must be reliably confirmed.