A-268 Comparison of the Elecsys® HCV Duo Assay to Standard of Care Algorithmic Testing
Authors: Bui-Bullock T , Brown A P , Brown M , Lawless S , Roemmich B , Anderson N W , Farnsworth C W 
Published: October 2024

Abstract

Background
Traditional hepatitis C virus (HCV) testing methods, though effective, may miss crucial diagnostic opportunities. The goal of this study was to assess the utility of Elecsys® HCV Duo antibody/antigen (Ab/Ag) assay as an alternative to traditional HCV algorithmic testing in the United States.

Methods
A prospective study was conducted at Barnes Jewish Hospital in St. Louis, Missouri. Patients with concurrent HCV Ab and molecular testing ordered within 48 h were enrolled. A total of 1,351 remnant serum and plasma-EDTA specimens were frozen following standard of care testing, which consisted of the Abbott Architect anti-HCV assay with reflex to cobas® HCV molecular assay. Patient demographics, risk factors, and results from both standard of care and HCV Duo testing were recorded.

Results
Among 1351 specimens, the HCV positivity rate as defined by algorithm was 19.9% (269/1351). Risk factors including homelessness and prior intravenous drug use were significantly associated with HCV diagnosis (P&lt;0.0001). HCV Duo testing demonstrated a positivity rate of 19.6% (263/1345) based on Ab/Ag dual positivity. Comparing the HCV Duo Ab module to standard of care serology revealed a 95.1% PPA (95% CI, 93.1-96.5) and 98.8% NPA (95% CI, 97.7-99.4), while the HCV Duo Ag component exhibited a 72.3% PPA (95% CI, 66.7-77.3) and 99.6% NPA (95% CI, 99.1-99.9) when compared to molecular testing. In HCV-RNA+ patients, the Ag component was positively correlated to viral load with a Spearman r of 0.770 (95% CI, 0.715-0.815). The median viral load with for patients with Ag+ results was 6.27 log10 IU/mL (IQR, 5.90-6.69) and for patients with Ag- results was 5.08 log10 IU/mL (IQR, 4.47-5.61). Of HCV-RNA+ specimens , 266/271 (98.2%) were successfully detected on the Ab module. Among anti-HCV+/HCV-RNA+ cases, 99.2% (261/263) were detected as Ab+/Ag+ on the HCV Duo assay. These had a turnaround time (TAT) from serology to molecular results of 28.1 ± 23.5 h, which may have been significantly decreased if Ab/Ag dual positivity was solely used to establish a diagnosis (average TAT of 27 min). The remaining two discrepant specimens were from patients with a prior history of HCV infection, which may represent false negatives or seronegative chronic HCV infections. Notably, 5/8 (62.5%) anti-HCV-/HCV-RNA+ specimens were detected on the HCV Duo assay, which would have been missed by traditional algorithmic testing. These five patients had viral loads ranging from 323-41,400,000 IU/mL, compared to &lt;15-5,400 IU/mL in the three undetected specimens. Of these five additional patient specimens captured on HCV Duo, two patients received an organ from an HCV+ donor, while the remaining three had no known history of HCV infection or transplant from an HCV+ donor.

Conclusions
The Elecsys® HCV Duo Ab/Ag assay, with its high sensitivity and specificity, drastically shortens the diagnostic window. Importantly, it successfully identified several anti-HCV-/HCV-RNA+ cases, a subgroup often undiagnosed by current algorithmic testing, demonstrating promise for improved diagnostic efficiency and accuracy in HCV detection. Further investigation is needed to determine whether improved diagnostic efficiency is due to enhanced antibody or antigen detection.