Multicenter performance evaluation of the Elecsys HCV Duo immunoassay.

BACKGROUND: The diagnostic accuracy of the Elecsys® HCV Duo antigen-antibody combination immunoassay (Roche Diagnostics GmbH) was evaluated for the detection of hepatitis C virus (HCV) infection, versus commercially available comparators. METHODS: This multicenter study (August 2020-March 2021) assessed the specificity of the Elecsys HCV Duo immunoassay and comparator assays in blood donor and routine clinical laboratory samples; sensitivity was determined in confirmed HCV-positive samples and seroconversion panels. The Elecsys HCV Duo immunoassay was compared with the Monolisa HCV Ag-Ab ULTRA V2, Murex HCV Ag/Ab Combination and ARCHITECT HCV Ag assays, as well as nucleic acid testing (NAT). The antibody (anti-HCV) module of the Elecsys HCV Duo immunoassay was compared with the Elecsys Anti-HCV II, Alinity s Anti-HCV, ARCHITECT Anti-HCV and RIBA HCV 3.0 SIA assays. RESULTS: The specificity of the Elecsys HCV Duo immunoassay was 99.94% (95% confidence interval [CI], 99.89-99.97) and 99.92% (95% CI, 99.71-99.99) in blood donor (n = 20,634) and routine clinical laboratory samples (n = 2531), respectively. The specificity of the Elecsys HCV Duo immunoassay was similar or better than comparator assays. The sensitivity of the Elecsys HCV Duo immunoassay in confirmed HCV-positive samples (n = 257) was 99.6%. In seroconversion panels, the Elecsys HCV Duo immunoassay detected infections earlier (2.2-21.9 days) than all but one of the comparator assays and detected HCV 1.8 days later than NAT. CONCLUSIONS: The Elecsys HCV Duo immunoassay shows high diagnostic accuracy, reduces the diagnostic window, and could be used when NAT is not possible.

Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy.

INTRODUCTION AND OBJECTIVES: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. MATERIALS AND METHODS: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). RESULTS: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p < 0.001), intrahepatic HBV-DNA (ρ 0.73, p < 0.001) and plasma/serum HBV-DNA (ρ 0.80, p < 0.001), HBV-pgRNA (ρ 0.80, p < 0.001), and to lesser extend HBsAg (ρ 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up. CONCLUSIONS: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime.