Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B

Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n = 52), immune clearance (IC group, n = 105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n = 97), HBeAg-negative quiescent group (ENQ group, n = 95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n = 55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r = 0.874, p <0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r = 0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r = 0.537, p <0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p <0.001) and HBsAg (5.05/5.96 log mIU/mL, p <0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.