Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
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: http://creativecommons.org/licenses/by-nc/4.0/
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 4
th Ring Middle Road, Beijing 100039, China.
yongpingyang@hotmail.com
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
Processing time: 175 Days and 20.5 Hours
BACKGROUND
Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.
AIM
To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.
METHODS
This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.
RESULTS
Level of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and 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.
CONCLUSION
HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.
Core tip: Hepatitis B core-related antigen (HBcrAg) is an excellent monitor of hepatic histological changes, especially in patients with chronic hepatitis B treated with nucleoside analogs. Baseline HBcrAg level and logarithmic reduction of HBcrAg at week 72 of treatment can predict and monitor the chance of achieving regression of liver fibrosis and histological improvement.
