Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2019; 25(32): 4764-4778
Published online Aug 28, 2019. doi: 10.3748/wjg.v25.i32.4764
On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B
Xiu-Juan Chang, Chao Sun, Yan Chen, Xiao-Dong Li, Zu-Jiang Yu, Zheng Dong, Wen-Lin Bai, Xiao-Dong Wang, Zhi-Qin Li, Da Chen, Wen-Juan Du, Hao Liao, Qi-Yu Jiang, Li-Jun Sun, Yin-Yin Li, Cui-Hong Zhang, Dong-Ping Xu, Yong-Ping Chen, Qin Li, Yong-Ping Yang
Xiu-Juan Chang, Yong-Ping Yang, Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China
Xiu-Juan Chang, Yan Chen, Zheng Dong, Wen-Lin Bai, Yin-Yin Li, Yong-Ping Yang, Department of Therapeutic Research for Liver Cancer, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Chao Sun, Yong-Ping Yang, Peking University 302 Clinical Medical School, Beijing 100039, China
Xiao-Dong Li, Qi-Yu Jiang, Li-Jun Sun, Cui-Hong Zhang, Dong-Ping Xu, Department of Research for Clinical Medicine, the Fifth Medical center of Chinese PLA General Hospital, Beijing 100039, China
Zu-Jiang Yu, Zhi-Qin Li, Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Xiao-Dong Wang, Yong-Ping Chen, Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Da Chen, Qin Li, Fuzhou Infectious Diseases Hospital, Fuzhou 350025, Fujian Province, China
Wen-Juan Du, Medical Department Training Graduate Office, Chinese PLA General Hospital, Beijing 100853, China
Hao Liao, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Author contributions: Yang YP, Li Q and Chen YP designed research; Chang XJ, Sun C, Chen Y, Li XD, Chen YP, Yu ZJ, Dong Z, Bai WL, Chen D, Wang XD, Li ZQ and Du WJ performed research; Liao H, Jiang QY, Li YY, Zhang CH and Xu DP contributed new reagents or analytic tools; Chang XJ, Sun C, Chen Y, Li XD, Yang YP and Sun LJ analyzed data; Yang YP, Li Q and Chang XJ wrote the paper; Yang YP, Li Q and Chen YP made critical revisions of manuscript.
Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme, No. 2013ZX10005002 and Beijing the Special Clinical Application Research and Translational Grants, No. Z151100004015221.
Institutional review board statement: This manuscript was approved by the institutional review board.
Clinical trial registration statement: The clinical trial have been registered (NCT01965418).
Informed consent statement: All patients signed informed consent statement.
Conflict-of-interest statement: Authors disclose no any conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Ping Yang, MD, PhD, Chief Doctor, Department of Therapeutic Research for Liver Cancer, the fifth Medical Center of Chinese PLA General Hospital, 100 Western 4th Ring Middle Road, Beijing 100039, China.
Telephone: +86-10-63879193 Fax: +86-10-63879193
Received: March 6, 2019
Peer-review started: March 6, 2019
First decision: April 11, 2019
Revised: May 14, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: August 28, 2019
Research background

Cirrhosis can lead to hepatocellular carcinoma, liver failure, even death. Early and accurate diagnosis of hepatic fibrosis/cirrhosis is pretty important for managing chronic hepatitis B (CHB) patients and preventing cirrhosis-related morbidity and mortality. Liver biopsy as the gold standard for fibrosis stage is invasive, poor acceptive, those limit its wide application. Many models for fibrosis stage have some limitations and few of them have been validated.

Research motivation

Some studies have reported that hepatitis B core-related antigen (HBcrAg) is closely related with liver fibrosis stage in CHB patients. However, whether HBcrAg can be a potential biomarker for assessing liver fibrosis stage and monitoring the change of liver histology after antivirus is unknown.

Research objectives

In this study, we aimed to evaluate the value of serum HBcrAg level in liver fibrosis stage and changes of liver histology after nucleos(t)ide analogues treated . If clarified, the liver fibrosis stage and fibrosis regression could be assessed and monitored by a non-invasive biomarker, serum HBcrAg level, without liver biopsy.

Research methods

Base on a prospective multicenter study, multiple ordinal regression analysis was used to screen variables associated with Ishak fibrosis score in 403 CHB patients, including 374 with entecavir for 72 wk (291 underwent paired liver biopsy) and 29 as controls. Multivariate regression analysis was used to explore key factors associated with fibrosis regression and histological improvement.

Research results

Serum HBcrAg level, basal core promoter/precore (BCP/PC) mutant, qHBsAg and platelet counts were independently associated with fibrosis staging on multiple ordinal regression. HBcrAg concentration > 6.33 log IU/mL at baseline and its logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.

Research conclusions

Serum HBcrAg level can assess liver fibrosis staging and monitor changes of liver histology, especially in CHB patients treated with nucleoside analogs.

Research perspectives

This study strongly suggests HBcrAg is an excellent non-invasive biomarker for assessing liver fibrosis staging and monitoring changes of liver histology. In order to more accurately assess liver fibrosis staging and predict fibrosis regression, the model including HBcrAg should be established in further research.