Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA

Danny Ka‐Ho Wong; Wai‐Kay Seto; Ka‐Shing Cheung; Chun‐Kong Chong; Fung‐Yu Huang; James Fung; Ching‐Lung Lai; M.‐F. Yuen

doi:10.1111/liv.13346

journal article Jan 28, 2017

Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA

Danny Ka‐Ho Wong Wai‐Kay Seto

Ka‐Shing Cheung Chun‐Kong Chong Fung‐Yu Huang James Fung

Ching‐Lung Lai M.‐F. Yuen

Liver International Vol. 37 No. 7 pp. 995-1001 · Wiley

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Abstract

AbstractBackground & AimsHepatitis 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.MethodsThree 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.ResultsHBcrAg 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).ConclusionsSerum 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.

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Details

Published: Jan 28, 2017
Vol/Issue: 37(7)
Pages: 995-1001
License: View

Authors

D

Danny Ka‐Ho Wong

Department of Medicine The University of Hong Kong Hong Kong SAR China; State Key Laboratory for Liver Research The University of Hong Kong Hong Kong SAR China

W

Wai‐Kay Seto

Department of Medicine The University of Hong Kong Hong Kong SAR China; State Key Laboratory for Liver Research The University of Hong Kong Hong Kong SAR China

K

Ka‐Shing Cheung

Department of Medicine The University of Hong Kong Hong Kong SAR China

C

Chun‐Kong Chong

Department of Medicine The University of Hong Kong Hong Kong SAR China

F

Fung‐Yu Huang

Department of Medicine The University of Hong Kong Hong Kong SAR China

J

James Fung

Department of Medicine The University of Hong Kong Hong Kong SAR China; State Key Laboratory for Liver Research The University of Hong Kong Hong Kong SAR China

C

Ching‐Lung Lai

Department of Medicine The University of Hong Kong Hong Kong SAR China; State Key Laboratory for Liver Research The University of Hong Kong Hong Kong SAR China

M

M.‐F. Yuen

Department of Medicine The University of Hong Kong Hong Kong SAR China; State Key Laboratory for Liver Research The University of Hong Kong Hong Kong SAR China

Funding

Fujirebio Inc.

Cite This Article

Danny Ka‐Ho Wong, Wai‐Kay Seto, Ka‐Shing Cheung, et al. (2017). Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA. Liver International, 37(7), 995-1001. https://doi.org/10.1111/liv.13346

Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA

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