Advancing HBV Diagnostics: The Role of Ultrasensitive HBsAg Testing

Hepatitis B virus (HBV) represents a significant global health challenge, affecting over 254 million individuals and contributing to 1.1 million deaths from liver-related complications in 2022. The World Health Organization has set ambitious targets to reduce HBV infections and mortality by 2030. However, only a small proportion (13%) of infected individuals receive timely diagnosis and treatment. HBV elimination efforts necessitate substantial improvements in HBV diagnosis, particularly in identifying occult HBV infections (OBI), early-stage infections, and breakthrough cases. The hepatitis B surface antigen (HBsAg) is a key biomarker in HBV diagnosis, serving as a reliable indicator of infection status and treatment response. Conventional HBsAg assays, with a lower limit of detection (LoD) between 0.03-250 IU/mL, often fail to detect OBI and HBV reactivation. In contrast, ultrasensitive HBsAg assays, with an LoD as low as 0.005 IU/mL, can improve the identification of low concentration levels of HBsAg, facilitating earlier diagnosis, monitoring of therapeutic response, and assessing for functional cure. Research confirms the superiority of ultrasensitive assays in detecting HBV in cases missed by conventional assays, detection of NAT-yield samples, and enabling earlier detection of HBV reactivation. This review examines the challenges in HBV diagnostics and the clinical utility of ultrasensitive HBsAg assays in improving progress toward global HBV elimination.