Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA. (28th January 2017)

• Record Type: Journal Article
• Authors: Wong, Danny Ka‐Ho; Seto, Wai‐Kay; Cheung, Ka‐Shing; Chong, Chun‐Kong; Huang, Fung‐Yu; Fung, James; Lai, Ching‐Lung; Yuen, Man‐Fung
• Is Part Of: Liver international. Volume 37:Number 7(2017)
• Page Start: 995
• Page End: 1001
• Publication Date: 2017-01-28
• Subjects: covalently closed circular DNA -- hepatitis B -- hepatitis B core‐related antigen -- hepatitis B serum markers -- intrahepatic HBV DNA; Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.13346
• Languages: English
• ISSNs: 1478-3223

Abstract

Abstract: Background & Aims: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key to viral persistence in chronic hepatitis B infection. Serum hepatitis B core‐related antigen (HBcrAg) is a novel marker for HBV disease. We aimed to determine whether HBcrAg could be a surrogate marker for intrahepatic cccDNA. Methods: Three hundred and five liver biopsies and the corresponding sera collected from 138 nucleos(t)ide analogues‐treated patients were analysed. 124 patients had paired liver biopsies at baseline and 1‐year post‐treatment, and 43 patients had a third biopsy after 6‐12 years of treatment. Serum HBcrAg, HBV DNA and hepatitis B surface antigen (HBsAg), and intrahepatic HBV DNA and cccDNA were measured. Results: HBcrAg strongly correlated with cccDNA ( r =.70), intrahepatic total HBV DNA ( r =.67) and serum HBV DNA ( r =.69; all P <.0001). In the 130 samples with undetectable serum HBV DNA, HBcrAg was detectable in 101 (78%) samples, and HBcrAg levels still correlated positively with cccDNA ( r =.42, P <.0001). At ≥6 years of therapy, the median logarithmic reduction in HBcrAg was 2.7 log kU/mL, which was comparable to the magnitude of reduction in cccDNA. Twenty‐one patients had undetectable cccDNA after ≥6 years of treatment, in whom 15 (71%) had detectable HBcrAg (range: 1.2‐537 kU/mL). Conclusions: Serum HBcrAg is a reliable surrogate marker for intrahepatic cccDNA. HBcrAg could be a very sensitive marker to reflect the cccDNA content and persistence of disease even with the cccDNA levels below the detection limit of assays.