Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 8, 2016; 8(34): 1511-1520
Published online Dec 8, 2016. doi: 10.4254/wjh.v8.i34.1511
On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B
Yu-Hua Gao, Qing-Hua Meng, Zhan-Qing Zhang, Ping Zhao, Qing-Hua Shang, Quan Yuan, Yao Li, Juan Deng, Tong Li, Xue-En Liu, Hui Zhuang
Yu-Hua Gao, Yao Li, Juan Deng, Tong Li, Xue-En Liu, Hui Zhuang, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Qing-Hua Meng, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
Zhan-Qing Zhang, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Ping Zhao, Department of Hepatology, 302 Military Hospital of China, Beijing 100039, China
Qing-Hua Shang, Department of Hepatology, the No.88 Hospital of the People’s Liberation Army, Taian 271000, Shandong Province, China
Quan Yuan, National Institute of Diagnostic and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361000, Fujian Province, China
Author contributions: Liu XE and Zhuang H designed the study; Gao YH and Li Y performed the experiments; Meng QH, Zhang ZQ, Zhao P, Shang QH, Yuan Q, Deng J and Li T were involved in samples collection and database establishment; Gao YH analyzed data and wrote the manuscript; Liu XE edit the manuscript for important contents; Zhuang H critically revised the manuscript; all authors have read and approved the final version of the manuscript.
Supported by Major Science and Technology Special Project of China Twelfth Five-year Plan, Nos. 2013ZX10002004 and 2012ZX10002003.
Institutional review board statement: The study was approved by the Institutional Review Board of Peking University Health Science Center.
Informed consent statement: All recruited patients signed written informed consents.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: Xue-En Liu, MD, Associate Professor, Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. xueenliu@bjmu.edu.cn
Telephone: +86-10-82802413 Fax: +86-10-82802413
Received: August 12, 2016
Peer-review started: August 13, 2016
First decision: September 13, 2016
Revised: September 26, 2016
Accepted: October 22, 2016
Article in press: October 24, 2016
Published online: December 8, 2016
Abstract
AIM

To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

METHODS

Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated.

RESULTS

Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer < -0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928.

CONCLUSION

The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.

Keywords: Response predictor, Quantitative detection, Hepatitis B e antigen, Hepatitis B virus DNA, Chronic hepatitis B, Nucleos(t)ide analogues

Core tip: Few studies have systematically evaluated quantitative hepatitis B surface antigen, hepatitis B e antigen (HBeAg), hepatitis B core antibody, hepatitis B virus DNA and alanine aminotransferase for predicting treatment response to nucleos(t)ide analogues (NAs) in HBeAg-positive chronic hepatitis B (CHB). In this study, on-treatment HBeAg level as well as its declined value at 24-wk were identified to be the best predictors not only for 96-wk virological response (VR) but also for HBeAg seroconversion (SC). The combination of HBeAg level and its decline at 24-wk strongly predicted 96-wk VR and HBeAg SC with the AUROC of 0.923 and 0.928, respectively. Thus monitoring an early on-treatment HBeAg level and its decline may help to optimize NAs therapy for CHB patients.