Three heads are better than two: Hepatitis B core-related antigen as a new predictor of hepatitis B virus-related hepatocellular carcinoma
Open Access
- 1 October 2021
- journal article
- review article
- Published by The Korean Association for the Study of the Liver in Clinical and Molecular Hepatology
- Vol. 27 (4), 524-534
- https://doi.org/10.3350/cmh.2021.0012
Abstract
Patients with chronic hepatitis B virus (HBV) infection are at risk of developing hepatocellular carcinoma (HCC), and serum markers reflecting viral replication are potential predictors for HCC development. Besides the levels of serum HBV DNA and hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) quantification is an emerging serological marker for viral replication. Unlike HBV DNA and HBsAg, HBcrAg is a covalently closed circular DNA-derived protein marker, consisting of hepatitis B e antigen (HBeAg), p22cr, and hepatitis B core antigen. In treatment-naive HBV patients, higher HBcrAg levels are shown to be associated with an increased risk of HCC in several studies. More importantly, HBcrAg may complement HBV DNA level to predict HCC development. For example, an Asian treatment-naive cohort study's data showed that HBcrAg level of 4 log U/mL was effective to stratify HCC risk in HBeAg-negative patients with intermediate viral loads, who may not need antiviral therapy because of the low to moderate risk of HCC. In patients receiving prolonged nucleos(t)ide analogue with profound viral suppression, most data indicated that HBV DNA and HBsAg levels no longer serve as HCC predictors. However, several studies suggested on-treatment HBcrAg levels may remain as an HCC predictor. In summary, HBcrAg level can be a useful biomarker for treatment-naive patients, but its value in on-treatment patients needs validation. The next challenge is how to combine HBcrAg with the other viral markers to construct a better HCC prediction model, optimizing the management of HBV patients.Keywords
Funding Information
- National Taiwan University Hospital (107-N4041 ,108-N4157 ,109-N4644 ,109-P05)
- Ministry of Science and Technology, Taiwan (106-2314-B-002-136)
- National Health Research Institutes (EX108-10807BC)
This publication has 43 references indexed in Scilit:
- New insight in the pathobiology of hepatitis B virus infectionGut, 2012
- Associations Between Hepatitis B Virus Mutations and the Risk of Hepatocellular Carcinoma: A Meta-AnalysisJNCI Journal of the National Cancer Institute, 2009
- Correlation between serum hepatitis B virus core‐related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patientsJournal of Medical Virology, 2008
- Associations Between Hepatitis B Virus Genotype and Mutants and the Risk of Hepatocellular CarcinomaJNCI Journal of the National Cancer Institute, 2008
- Hepatitis B Virus DNA-negative Dane Particles Lack Core Protein but Contain a 22-kDa Precore Protein without C-terminal Arginine-rich DomainOnline Journal of Public Health Informatics, 2005
- Prevalence of HBV precore/core promoter variants in the United StatesHepatology, 2003
- Relationship between the Development of Precore and Core Promoter Mutations and Hepatitis B e Antigen Seroconversion in Patients with Chronic Hepatitis B VirusThe Journal of Infectious Diseases, 2002
- Different hepatitis b virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversionHepatology, 1999
- High prevalence of 1762T 1764A mutations in the basic core promoter of hepatitis B virus isolated from black africans with hepatocellular carcinoma compared with asymptomatic carriersHepatology, 1999
- Predictive value of precore hepatitis B virus mutations in spontaneous and interferon-induced hepatitis B e antigen clearanceHepatology, 1995