Distinct patterns of serum hepatitis B core-related antigen during the natural history of chronic hepatitis B.

BACKGROUND: 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. Here, we aimed to characterize HBcrAg during the natural course of CHB. METHODS: Four-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. RESULTS: HBcrAg, 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. CONCLUSION: HBcrAg 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.

Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients.

The objective of this study was to evaluate the validities of serum hepatitis B core-related antigen (HBcrAg) for predicting the pathological status of liver tissues of chronic hepatitis B (CHB). A total of 205 Chinese patients with CHB, including 121 HBeAg-positive and 84 HBeAg-negative patients, were enrolled in this study. In HBeAg-positive patients, AUCs of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis were greater than 0.70; using serum HBcrAg<=4.81×10(4)kUmL(-1) and <=2.45×10(4)kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting severe necro-inflammation and advanced fbrosis were 0.697, 0.716, 0.711 and 0.818, 0.778, 0.785, respectively. In HBeAg-negative patients, the AUCs of serum HBcrAg for predicting significant necro-inflammation and significant fibrosis were greater than 0.70; using serum HBcrAg>=1.70×10(2)kUmL(-1) and >=4.02kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting significant necro-inflammation and significant fibrosis were 0.929, 0.964, 0.952 and 1.000, 1.000, 1.000, respectively. These results indicated favorable performances of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis in HBeAg-positive patients and significant necro-inflammation and significant fibrosis in negative patients.