Chi XM, Wang XM, Wang ZF, Wu RH, Gao XZ, Xu HQ, Ding YH, Niu JQ. Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B. World J Gastroenterol 2021; 27(40): 6927-6938 [PMID: 34790015 DOI: 10.3748/wjg.v27.i40.6927]
Corresponding Author of This Article
Jun-Qi Niu, MD, PhD, Academic Research, Dean, Director, Doctor, Professor, Research Scientist, Department of Hepatology, Key Laboratory of Zoonosis Research, Ministry Education, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, Jilin Province, China. junqiniu@jlu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
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Chi XM, Wang XM, Wang ZF, Wu RH, Gao XZ, Xu HQ, Ding YH, Niu JQ. Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B. World J Gastroenterol 2021; 27(40): 6927-6938 [PMID: 34790015 DOI: 10.3748/wjg.v27.i40.6927]
Xiu-Mei Chi, Xiao-Mei Wang, Zhong-Feng Wang, Rui-Hong Wu, Xiu-Zhu Gao, Hong-Qin Xu, Jun-Qi Niu, Department of Hepatology, Key Laboratory of Zoonosis Research, Ministry Education, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Xiu-Mei Chi, Yan-Hua Ding, Phase I Clinical Trials Unit, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Chi XM contributed to design and data analysis and drafted the manuscript; Wang XM contributed to data analysis and critically revised the manuscript; Wang ZF, Wu RH, Gao XZ and Xu HQ contributed to data acquisition and analysis; Ding YH critically revised the manuscript; Niu JQ contributed to the conception and critically revised the manuscript; All authors read and approved the final manuscript.
Supported byNational Science and Technology Major Project, No. 2017ZX10302201, No. 2017ZX09304004 and No. 2014ZX10002002; and National Program on Key Basic Research Project (973 Program), No. 2015CB554304.
Institutional review board statement: This study was approved by the ethics committee of the First Hospital of Jilin University.
Informed consent statement: Informed consent was obtained from each patient for the original trials, with clauses for possibly secondary analyses. The original studies were registered (ClinicalTrials.gov NCT03509688 and NCT03546530).
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Corresponding author: Jun-Qi Niu, MD, PhD, Academic Research, Dean, Director, Doctor, Professor, Research Scientist, Department of Hepatology, Key Laboratory of Zoonosis Research, Ministry Education, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, Jilin Province, China. junqiniu@jlu.edu.cn
Received: March 11, 2021 Peer-review started: March 11, 2021 First decision: April 5, 2021 Revised: May 6, 2021 Accepted: September 1, 2021 Article in press: September 1, 2021 Published online: October 28, 2021 Processing time: 229 Days and 7.6 Hours
Abstract
BACKGROUND
Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application.
AIM
The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion.
METHODS
This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530). Serum qHBcrAg, pgRNA, HBV DNA, hepatitis B core antigen, HBeAg, liver cccDNA, and HBV DNA were measured. The correlations of serum qHBcrAg with other biomarkers were analyzed.
RESULTS
A total of 139 patients were included. The mean qHBcrAg levels were 5.32 ± 1.18 log10 U/mL at baseline and decreased during treatment (all P < 0.0001). Serum qHBcrAg levels were positively correlated with pgRNA (r = 0.597, P < 0.0001) and cccDNA (r = 0.527, P < 0.0001) levels. The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant (r = 0.399, P < 0.0001). HBcrAg predicted HBeAg seroconversion, with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion [odds ratio (OR) = 2.402, 95% confidence interval (CI): 1.314-4.391, P = 0.004; OR = 3.587, 95%CI: 1.315-9.784, P = 0.013].
CONCLUSION
Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.
Core Tip: The mean quantitative hepatitis B core-related antigen (qHBcrAg) levels were decreased post treatment. Serum qHBcrAg levels were positively associated with pregenomic RNA and covalently closed circular DNA levels. qHBcrAg predicted hepatitis B e antigen (HBeAg) seroconversion with an area under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log qHBcrAg at wk 24 and wk 48 was independently associated with HBeAg seroconversion (odds ratio = 2.402, 95% confidence interval: 1.314-4.391, P = 0.004; odds ratio = 3.587, 95% confidence interval: 1.315-9.784, P = 0.013, respectively).
