Indexed on: 16 Apr '20Published on: 16 Apr '20Published in: Journal of Gastroenterology and Hepatology
Hepatitis B core related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in 3 serial serum samples for each patient. Patients were divided into 6 groups for analysis: HBeAg-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI) and HBsAg seroclearance (SS). 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with HBV DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥6.0 log U/ml could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve [AUROC] 0.99, p<0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥4.0 log U/ml could best differentiate ENH from ENI (AUROC 0.81; p<0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63% and 89% patients in ENH, ENI, and SS groups at the last visit, respectively. HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease. © 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.