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
ARTICLE HIGHLIGHTS
Research Background

Hepatitis B surface antigen (HBsAg) levels have been studied in the natural course and pegylated interferon treatment course. During nucleos(t)ide analogue (NA) therapy, there are still controversies about using HBsAg to predict treatment responses, especially in HBeAg-negative patients. Besides, HBsAg kinetics and its relationships with outcomes during long-term entecavir therapy have not been fully elucidated.

Research motivation

We hoped to elucidate the utility of HBsAg in the prediction of treatment response in HBeAg-positive and HBeAg-negative patients. Furthermore, we would like to demonstrate the detailed HBsAg kinetics among different disease statuses and their relationships with the treatment outcomes.

Research objectives

We aimed to investigate the utility and kinetics of serum HBsAg in chronic hepatitis B patients during long-term entecavir treatment.

Research methods

We conducted this retrospective study to analyze the relationships between HBsAg levels and treatment responses in treatment-naïve chronic hepatitis B patients receiving at least two 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. Serum HBsAg levels were determined at baseline, one year and five year time points. The cumulative incidence of treatment responses were obtained using the Kaplan-Meier analysis. Multivariate analysis was performed using Cox proportional hazards regression. A linear mixed model with a random intercept was used for analysis of longitudinal changes of HBsAg levels.

Research results

We demonstrated that baseline HBsAg levels could be used to predict treatment responses in HBeAg-positive patients with a cut-off value of 4 log IU/mL and in HBeAg-negative non-cirrhotic patients with a cut-off value of 2.4 log IU/mL. Furthermore, our study provides a global view of HBsAg kinetics in chronic hepatitis B patients during long-term entecavir therapy. The HBeAg-positive non-cirrhotic group had the highest HBsAg levels at the baseline and throughout entecavir treatment, as compared with the other three patient groups. Higher rates of HBsAg decrease were observed in the first year for patients with higher baseline HBsAg levels. A rapid HBsAg decline did not necessarily guarantee better outcomes

Research conclusions

Baseline HBsAg levels could be used to predict virological, serological, and biochemical responses. In the interpretation of HBsAg changes, HBeAg levels and decrease rates should be considered together according to a patient’s disease status.

Research perspectives

HBsAg is a useful biomarker for chronic hepatitis B patients receiving NA therapy. It deserves to be studied in large prospective cohorts with different comorbidities for the future research.