Abstract
BackgroundThe current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence. Quantified assays for hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold promise for further optimization of therapy. Here, we aimed to characterize HBcrAg during the natural course of CHB.MethodsFour-hundred and forty four treatment naïve CHB patients, who all underwent liver histology examination, were enrolled in this cross-sectional study. Their HBV DNA, HBsAg, HBeAg and HBcrAg titres were quantified and analyzed in the context of four distinct clinical phases. Correlation of HBcrAg and HBsAg with other markers were performed. The relationship between liver and serum antigen levels were also assessed.ResultsHBcrAg, like HBsAg, exhibited high degree of correlation with HBV DNA. However, a more significant linear relationship was found between HBcrAg and HBeAg titre in immune tolerant (IT) and immune clearance (IC) phases, while in HBeAg negative hepatitis (ENH) group, HBV DNA is a major determinant of HBcrAg. Significant difference was observed in liver HBcAg score and HBcrAg level in both IT and IC phases whereas barely significant positive correlations between liver HBsAg score and HBsAg titre was documented.ConclusionHBcrAg titre exhibited distinct correlative profile in a phase-specific manner. In addition, its level is well-related to the intrahepatic expression of core antigen. It has a considerable utility in monitoring and refining antiviral therapy.
Highlights
The current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence
A deeper understanding of the pathogenesis and natural history of CHB has been facilitated by the improved sensitivity of Hepatitis B virus (HBV) DNA viral load assays, reliable assays for serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) [2, 3] and the development of assays for the detection and measurement of HBV intrahepatic reservoir, covalently closed circular DNA [4]
By multiple linear regression, that the major variance of hepatitis B corerelated antigen (HBcrAg) can be attributed to HBeAg in IT and IC groups, while in e antigen negative hepatitis (ENH) group, HBV DNA is a major determinant of HBcrAg
Summary
The current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence. Quantified assays for hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold promise for further optimization of therapy. A deeper understanding of the pathogenesis and natural history of CHB has been facilitated by the improved sensitivity of HBV DNA viral load assays, reliable assays for serum hepatitis B surface antigen (HBsAg) and HBeAg [2, 3] and the development of assays for the detection and measurement of HBV intrahepatic reservoir, covalently closed circular DNA (cccDNA) [4]. It has been shown to have close correlation with HBV DNA but exhibit less decline after antiviral therapy [7] It was proposed as a surrogate marker for HBV persistence [8]
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