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

Abstract

Background: Changes in two novel HBV serologic 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. Methods: Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analyzed cross-sectionally. Patients were categorized into 5 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. Results: 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 ENH-group (r=0.268, p=0.008). HBcrAg correlated best with HBV DNA in ENQ-group (r=0.537, p<0.001). 42.1% of ENQ-group patients had undetectable HBcrAg; this subgroup of patients, when compared to 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. 40% 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 SC-group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7%/36.4% respectively, p=0.284 and 76.5/93.2 months respectively, p=0.245). Conclusion: 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.