Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2017; 23(16): 2978-2986
Published online Apr 28, 2017. doi: 10.3748/wjg.v23.i16.2978
Early hepatitis B viral DNA clearance predicts treatment response at week 96
Xiao-Yu Fu, De-Ming Tan, Cui-Mei Liu, Bin Gu, Li-Hua Hu, Zhong-Tian Peng, Bin Chen, Yuan-Lin Xie, Huan-Yu Gong, Xiao-Xuan Hu, Lian-Hui Yao, Xiao-Ping Xu, Zheng-Yuan Fu, Lang-Qiu He, Si-Hai Li, Yun-Zhu Long, De-Hui Li, Ji-Long Gu, Shi-Fang Peng
Xiao-Yu Fu, De-Ming Tan, Cui-Mei Liu, Shi-Fang Peng, Key Laboratory of Viral Hepatitis, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Bin Gu, The Second People’s Hospital of Chenzhou, Chenzhou 423000, Hunan Province, China
Li-Hua Hu, The Third People’s Hospital of Hengyang, Hengyang 421005, Hunan Province, China
Zhong-Tian Peng, The First Affiliated Hospital of Nanhua University, Hengyang 421001, Hunan Province, China
Bin Chen, The First Affiliated Hospital of Hunan Traditional Chinese Medicine University, Changsha 430100, Hunan Province, China
Yuan-Lin Xie, The First Hospital of Changsha, Changsha 430100, Hunan Province, China
Huan-Yu Gong, The Third Xiangya Hospital, Changsha 410008, Hunan Province, China
Xiao-Xuan Hu, The People’s Hospital of Hunan Province, Changsha 410005, Hunan Province, China
Lian-Hui Yao, Wangwang Hospital of Changsha, Changsha 410005, Hunan Province, China
Xiao-Ping Xu, The People’s Hospital of Xiangxi, Jishou 416000, Hunan Province, China
Zheng-Yuan Fu, The First People’s Hospital of Huaihua, Huaihua 418000, Hunan Province, China
Lang-Qiu He, The Central Hospital of Xiangtan, Xiangtan 411100, Hunan Province, China
Si-Hai Li, The First People’s Hospital of Yueyang, Yueyang 414000, Hunan Province, China
Yun-Zhu Long, The Central Hospital of Zhuzhou, Zhuzhou 412007, Hunan Province, China
De-Hui Li, The First People’s Hospital of Changde, Changde 415003, Hunan Province, China
Ji-Long Gu, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
Author contributions: All authors contributed to the study.
Supported by the National High Technology Research and Development Program (863 Program), No. 2012AA022605.
Institutional review board statement: This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital, Central South University, Hunan, China.
Clinical trial registration statement: This is an observational study rather than a clinical trial. All patients received nucleoside (acid) analogues according to the guidelines.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no 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/
Correspondence to: Shi-Fang Peng, PhD, Key Laboratory of Viral Hepatitis, Department of Infectious Diseases, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China. 917940984@qq.com
Telephone: +86-731-84327221 Fax: +86-731-84327228
Received: December 21, 2016
Peer-review started: December 23, 2016
First decision: January 19, 2017
Revised: February 18, 2017
Accepted: March 15, 2017
Article in press: March 15, 2017
Published online: April 28, 2017
Processing time: 127 Days and 17.1 Hours
Abstract
AIM

To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B.

METHODS

A total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response.

RESULTS

The rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk.

CONCLUSION

Hepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

Keywords: Chronic hepatitis B; Nucleoside analogue; Viral DNA load; Hepatitis B antigens; Hepatitis B antibodies; Hepatitis B virus DNA; Hepatitis B virus

Core tip: Elimination of the hepatitis B surface antigen is the ultimate goal of antiviral therapy; however, this goal is rarely achieved. Complete suppression of hepatitis B virus (HBV) DNA is the current goal of antiviral therapy. Early determination of patients who are not likely to respond to chronic antiviral therapy may help providers make appropriate, timely changes. This study demonstrated a 100% complete DNA response and approximately 50% hepatitis B envelope antigen seroconversion at week 96 when the HBV DNA was suppressed to < 10 IU/mL at week 24. For patients who do not achieve HBV DNA < 10 IU/mL at week 24, add-on or alternative therapies should be considered.