Time to Positivity of a Rapid HB s A g Assay as a Surrogate Marker of Quantitative HB s A g: Multicentre Proof‐of‐Concept Study

Abstract

BACKGROUND AND AIMS: Point-of-care (POC) diagnostics for hepatitis B virus (HBV) are limited to qualitative results. This study evaluated whether the time to positivity of a rapid HBsAg assay could serve as a surrogate marker of quantitative HBsAg (qHBsAg) and virological activity. METHODS: This multicentre, prospective proof-of-concept study included cohorts from Spain and Ethiopia. Adults with chronic or resolved HBV infection and healthy controls were enrolled. Paired venous and capillary blood samples were collected; capillary blood was tested with Determine HBsAg2 rapid test recording time to positivity, while qHBsAg and HBV DNA were measured using immunoassay and PCR, respectively. RESULTS: A total of 513 HBsAg-positive individuals were included (263 Spain; 250 Ethiopia). All healthy controls and individuals with resolved infection tested negative. Time to positivity showed an inverse correlation with qHBsAg in both cohorts (Spain: r = -0.749; Ethiopia: r = -0.374; p < 0.001 for both). No association was observed between time to positivity and HBV DNA levels. The performance to identify patients with HBsAg levels < 1000 IU/mL was higher in Spain (AUROC 0.86) than in Ethiopia (AUROC 0.65). Better performance was observed for detecting HBsAg levels < 100 IU/mL in both countries (AUROC 0.96 and 0.77, respectively). CONCLUSIONS: Time to positivity in a rapid HBsAg assay correlated inversely with qHBsAg and may provide a simple, semi-quantitative estimate of antigen burden. Although unrelated to HBV DNA, it could expand the utility of point-of-care HBsAg testing beyond qualitative diagnosis, particularly where quantitative HBsAg assays are unavailable.