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Summary
Background
Chronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification of intrahepatic cccDNA requires liver biopsies, serological markers can be non‐invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core‐related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.
Aim
To examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.
Methods
We reviewed all papers published in the PubMed journal list and s from major international meetings that included the keyword “HBcrAg” or “hepatitis B core‐related antigen” until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors’ experience.
Results
HBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg‐negative chronic hepatitis from HBeAg‐negative chronic infection, predicting spontaneous or treatment‐induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post‐operative HCC recurrence.
Conclusions
HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.
Linked Content
This article is linked to Wang et al and Mak and Yuen papers. To view these articles visit https://doi.org/10.1111/apt.14673 and https://doi.org/10.1111/apt.14684.