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
Processing time: 101 Days and 21.6 Hours
ARTICLE HIGHLIGHTS
Research background

Nucleos(t)ide analogues (NAs) only suppress hepatitis B virus (HBV) DNA replication, resulting in decreased serum HBV DNA, but they do not suppress covalently closed circular DNA (cccDNA). Pregenome RNA (pgRNA) is the direct product of cccDNA. A number of studies have shown that HBV RNA levels in serum were related to virological response (VR) and prognosis. However, characteristics of alterations of serum HBV RNA in different chronic hepatitis B (CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.

Research motivation

In this work, we investigated the characteristics of HBV RNA alterations in CHB patients with different treatment effects. The relationships of HBV RNA with other serological markers were also analyzed. Finally, we calculated the predictive value of HBV RNA in anticipating HBeAg seroconversion. Solving these problems helps to investigate the predictive value of HBV RNA.

Research objectives

If HBV DNA is maintained at undetectable levels, it is difficult to predict whether a patient will have a serological response. To address this question, we evaluated whether HBV RNA had a relationship with VR and HBeAg antigen seroconversion, how HBV RNA was related to other indicators, whether HBV RNA was an independent indicator of HBeAg seroconversion, and finally, the diagnostic value of HBV RNA.

Research methods

The present study evaluated 61 CHB patients from September 2006 to December 2007 at the Department of Infectious Diseases of Peking University First Hospital (China) who had begun long-term entecavir (ETV) monotherapy. Finally, we collected 30 treatment-naive individuals. Serum HBV RNA was 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.

Research results

By comparing the dynamic characteristics of HBV RNA in the VR and partial VR groups, we found that HBV RNA showed a strong decrease in the VR group. By contrast, HBV RNA increased in the partial VR group. The serum HBV RNA level increased in the HBeAg no-seroconversion group compared with the HBeAg seroconversion group. Overall, HBsAg had a poor correlation with HBV RNA (r = 0.265, P = 0.041), and HBV DNA and HBV RNA did not show a correlation (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent predictor of HBeAg seroconversion and VR. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.

Research conclusions

In conclusion, we found that serum HBV RNA predicted both VR and HBeAg seroconversion. The data appeared to suggest that serum HBV RNA decreased in patients who achieved a VR during ETV therapy, and vice versa. Overall, HBsAg and HBV RNA had a poor correlation (r = 0.265, P = 0.041), and HBV DNA had no correlation to HBV RNA (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent predictor of HBeAg seroconversion and VR. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.

Research perspectives

The present study suggested that serum HBV RNA decreased in patients who achieved a VR during ETV therapy, and vice versa. HBeAg seroconversion was more likely to be achieved for CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment. In the future, the study could focus on the application value of HBV RNA in CHB patients with disease progression.