Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2019; 25(6): 719-728
Published online Feb 14, 2019. doi: 10.3748/wjg.v25.i6.719
Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients
Hao Luo, Xia-Xia Zhang, Li-Hua Cao, Ning Tan, Qian Kang, Hong-Li Xi, Min Yu, Xiao-Yuan Xu
Hao Luo, Ning Tan, Qian Kang, Hong-Li Xi, Min Yu, Xiao-Yuan Xu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
Xia-Xia Zhang, Department of Gastroenterology, Capital Medical University Beijing Tiantan Hospital, Beijing 100070, China
Li-Hua Cao, Department of Infectious Diseases, the Third Hospital of Qinhuangdao, Qinhuangdao 066000, Hebei Province, China
Author contributions: Luo H and Zhang XX equally designed the research; Luo H performed the research, acquired and analyzed the data, and wrote the article; Cao LH and Xi HL analyzed the data; Tan N, Kang Q, and Yu M acquired the data; Xu XY edited, reviewed, and approved the final article.
Supported by the 13th Five-Year Plan, No. 2018ZX09206005-002.
Institutional review board statement: The study protocol conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethic Committee of Shanghai Jing An Central Hospital (Approval No. 090f51e6809a26e1 v1.0).
Informed consent statement: Patients who were enrolled in the work provided informed consent.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
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: Xiao-Yuan Xu, MD, Professor, Department of Infectious Diseases, Peking University First Hospital, 8 Xishiku Street, Beijing 100034, China. xiaoyuanxu6@163.com
Telephone: +86-10-83575787 Fax: +86-10-83575787
Received: November 5, 2018
Peer-review started: November 5, 2018
First decision: December 28, 2018
Revised: January 11, 2019
Accepted: January 18, 2019
Article in press: January 18, 2019
Published online: February 14, 2019

Characteristics of alterations of serum hepatitis B virus (HBV) RNA in different chronic hepatitis B (CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.


To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir (ETV) treatment when HBV DNA is undetectable.


The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital (China) from September 2006 to December 2007. Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR (RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.


Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response (VR) and partial VR (PVR) groups at baseline (P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy (P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg (r = 0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.


The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.

Keywords: Chronic hepatitis B, Hepatitis B virus RNA, Virological response, HBeAg seroconversion, Entecavir

Core tip: HBeAg seroconversion was more likely to be achieved for chronic hepatitis B patients with hepatitis B virus (HBV) RNA levels below 4.12 log10 copies/mL before treatment. In the partial virological response group, serum HBV RNA showed an increasing trend.