Background: An accurate, single-point differential diagnosis between HBeAg-negative infection (ENI) and chronic hepatitis B (CHB) is an unmet need. Aims: To assess the diagnostic value of the new hepatitis B core-related antigen (HBcrAg) assay. Methods: A retrospective anonymised data analysis was performed in a multicentre European (nine centres and six countries) cohort of 1582 consecutive HBsAg-positive/HBeAg-negative subjects classified according to EASL guidelines as: 550-CHB, 710-ENI and 322-GZ (grey-zone, HBV-DNA