Clinical Performance of the Elecsys HCV Duo Immunoassay Compared with a Standard-of-Care Algorithm Using Alinity Anti-HCV Screening and HCV RNA Confirmation.

Background/Objectives: The Elecsys HCV Duo immunoassay simultaneously detects HCV core antigen (HCV Ag) and anti-HCV antibodies in a single sample. We evaluated its clinical performance against a standard-of-care reference algorithm of anti-HCV antibody and HCV RNA testing. Methods: We retrospectively analyzed 1332 residual serum or plasma samples tested with reference HCV RNA assays and the Alinity i Anti-HCV assay. Samples were classified as reference-positive, indicating current or past HCV infection (n = 166; 88 RNA+/Ab+ with active infection and 78 RNA-/Ab+ with resolved or treated infection), or reference-negative (n = 1166; RNA-/Ab-), including 1000 randomly selected blood donor samples. All specimens were tested with the Elecsys HCV Duo (cobas® e 801, Roche Diagnostics). Positive and negative percent agreements (PPA and NPA) were calculated against the combined reference standard. Results were further analyzed by infection status and viral load. No HCV RNA+/anti-HCV- (window-period) specimens were available. Results: Overall agreement was high (PPA 98.8% [164/166; 95% CI, 95.7-99.9%]; NPA 99.9% [1165/1166; 95% CI, 99.5-100.0%]). Agreement of the anti-HCV component with the Alinity i Anti-HCV assay was identical (PPA 98.8%, NPA 99.9%). The HCV Duo Ag component showed a PPA of 60.2% (95% CI, 49.2-70.5%) and NPA of 99.0% (95% CI, 98.3-99.5%) against HCV RNA detection. The Ag module was also reactive in 12 of 78 (15.4%) RNA-/Ab+ specimens, all from previously treated patients; thus, 53 of 65 (81.5%) dual Ag/Ab-reactive specimens had detectable HCV RNA. HCV Ag positivity was highest at HCV RNA ≥106 IU/mL (77.4%, 41/53), compared with 32.1% (9/28) at 104-106 IU/mL and 42.9% (3/7) at <104 IU/mL. Receiver operating characteristic analysis of the Ag component yielded an area under the curve of 0.920 (95% CI, 0.904-0.934). Conclusions: The Elecsys HCV Duo demonstrated high overall agreement with the reference methods, supporting its potential as a single-step screening test for HCV infection. Most, but not all, dual Ag/Ab-reactive specimens were viremic, so this result may help prioritize anti-HCV-positive individuals for linkage to care; however, the assay does not replace HCV RNA testing, which remains necessary to confirm active infection, particularly in Ag-negative or previously treated individuals. Because no window-period specimens were included, the potential of the assay for earlier detection of acute infection could not be evaluated.