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Article: Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA

TitleHepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA
Authors
KeywordsCovalently closed circular DNA
Hepatitis B
Hepatitis B core‐related antigen
Hepatitis B serum markers
Intrahepatic HBV DNA
Issue Date2017
PublisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
Citation
Liver International, 2017, v. 37 n. 7, p. 995-1001 How to Cite?
AbstractBackground & 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.
Persistent Identifierhttp://hdl.handle.net/10722/237767
ISSN
2017 Impact Factor: 4.5
2015 SCImago Journal Rankings: 1.677
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, DKH-
dc.contributor.authorSeto, WKW-
dc.contributor.authorCheung, KSM-
dc.contributor.authorChong, CK-
dc.contributor.authorHuang, FY-
dc.contributor.authorFung, JYY-
dc.contributor.authorLai, CL-
dc.contributor.authorYuen, RMF-
dc.date.accessioned2017-01-20T02:28:16Z-
dc.date.available2017-01-20T02:28:16Z-
dc.date.issued2017-
dc.identifier.citationLiver International, 2017, v. 37 n. 7, p. 995-1001-
dc.identifier.issn1478-3223-
dc.identifier.urihttp://hdl.handle.net/10722/237767-
dc.description.abstractBackground & 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.-
dc.languageeng-
dc.publisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1-
dc.relation.ispartofLiver International-
dc.rightsThis is the peer reviewed version of the following article: Liver International, which has been published in final form at http://dx.doi.org/10.1111/liv.13346. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectCovalently closed circular DNA-
dc.subjectHepatitis B-
dc.subjectHepatitis B core‐related antigen-
dc.subjectHepatitis B serum markers-
dc.subjectIntrahepatic HBV DNA-
dc.titleHepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA-
dc.typeArticle-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailSeto, WKW: wkseto2@hku.hk-
dc.identifier.emailCheung, KSM: cks634@hku.hk-
dc.identifier.emailHuang, FY: fungyu@hkucc.hku.hk-
dc.identifier.emailFung, JYY: jfung@hkucc.hku.hk-
dc.identifier.emailLai, CL: hrmelcl@hku.hk-
dc.identifier.emailYuen, RMF: mfyuen@hku.hk-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authoritySeto, WKW=rp01659-
dc.identifier.authorityCheung, KSM=rp02532-
dc.identifier.authorityFung, JYY=rp00518-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.authorityYuen, RMF=rp00479-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/liv.13346-
dc.identifier.pmid27992681-
dc.identifier.scopuseid_2-s2.0-85010988919-
dc.identifier.hkuros271014-
dc.identifier.volume37-
dc.identifier.issue7-
dc.identifier.spage995-
dc.identifier.epage1001-
dc.identifier.isiWOS:000403922800008-
dc.publisher.placeUnited States-

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