Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2018; 24(6): 725-736
Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.725
Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy
Tien-Ching Lin, Yen-Cheng Chiu, Hung-Chih Chiu, Wen-Chun Liu, Pin-Nan Cheng, Chiung-Yu Chen, Ting-Tsung Chang, I-Chin Wu
Tien-Ching Lin, Yen-Cheng Chiu, Hung-Chih Chiu, Pin-Nan Cheng, Chiung-Yu Chen, Ting-Tsung Chang, I-Chin Wu, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, 70403, Taiwan
Wen-Chun Liu, Ting-Tsung Chang, I-Chin Wu, Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan 70403, Taiwan
Author contributions: Lin TC collected the data, performed statistical analysis, and wrote the manuscript; Chiu YC, Chiu HC, Cheng PN and Chen CY provided the clinical samples; Liu WC performed HBsAg quantification and HBV genotyping; Chang TT directed the study; Wu IC designed the study, performed statistical analysis, and wrote the manuscript.
Institutional review board statement: This study was approved by the Institutional Review Board of National Cheng Kung University Hospital.
Informed consent statement: Informed consents were obtained at the request of the Institutional Review Board of National Cheng Kung University Hospital.
Conflict-of-interest statement: The authors declare that they have no conflicts 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/
Correspondence to: I-Chin Wu, MD, PhD, Assistant Professor, Department of Internal Medicine, National Cheng Kung University Hospital, No. 138 Sheng-Li Road, Tainan 70403, Taiwan. wichin@mail.ncku.edu.tw
Telephone: +886-6-2353535-3588 Fax: +886-6-2743166
Received: October 17, 2017
Peer-review started: October 18, 2017
First decision: November 8, 2017
Revised: November 17, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: February 14, 2018
Processing time: 111 Days and 15.3 Hours
Abstract
AIM

To investigate the utility of hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.

METHODS

This retrospective study included treatment-naïve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, one-year and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.

RESULTS

A total of 211 patients were enrolled. The median treatment time was 5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients (cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.

CONCLUSION

Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Keywords: Chronic hepatitis B; Entecavir; Hepatitis B e antigen; Hepatitis B surface antigen; Kinetics

Core tip: Baseline hepatitis B surface antigen (HbsAg) levels could be used to predict virological, serological, and biochemical responses during entecavir treatment. HBeAg-positive non-cirrhotic patients had the highest HBsAg levels at the baseline and throughout entecavir treatment, and had the highest HBsAg decrease rates during the first year of entecavir treatment. HBsAg levels decrease slowly during the treatment. Therefore, HBsAg should be checked at a 1-year interval if hepatitis B virus DNA remains undetectable. A rapid HBsAg decline per se did not achieve better patient outcomes. In the interpretation of HBsAg changes, HBsAg levels and decrease rates should be considered together according to disease status.