Retrospective Cohort Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2016; 22(47): 10388-10397
Published online Dec 21, 2016. doi: 10.3748/wjg.v22.i47.10388
Clinical features of acute hepatitis E super-infections on chronic hepatitis B
Chong Chen, Shu-Ye Zhang, Dan-Dan Zhang, Xin-Yan Li, Yu-Ling Zhang, Wei-Xia Li, Jing-Jing Yan, Min Wang, Jing-Na Xun, Chuan Lu, Yun Ling, Yu-Xian Huang, Liang Chen
Chong Chen, Liang Chen, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Chong Chen, Shu-Ye Zhang, Dan-Dan Zhang, Xin-Yan Li, Yu-Ling Zhang, Wei-Xia Li, Jing-Jing Yan, Min Wang, Jing-Na Xun, Chuan Lu, Yun Ling, Yu-Xian Huang, Liang Chen, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Shu-Ye Zhang, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China
Yu-Ling Zhang, Jing-Na Xun, School of Life Sciences, Hebei Normal University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Chen C and Zhang SY contributed equally to this work; Chen C acquired, analyzed and interpreted the data, and drafted the manuscript; Zhang SY conceived of and designed the study, interpreted the data, drafted the manuscript; Zhang DD, Li XY, Zhang YL, Li WX, Yan JJ, Wang M, Xun JN, Lu C, Ling Y and Huang YX provided technical support and contributed to the acquisition of data; Chen L conceived of and designed the study, performed critical revision of the manuscript for important intellectual content, provided administrative, technical or material support, supervised the study and obtained support funding.
Supported by National Program on Key Basic Research Project (973 Program), No. 2015CB554300 (to Zhang SY); the Joint Research Program for Emerging Frontier Technology in the Municipal Hospital of Shanghai, China, No. SHDC12015129.
Institutional review board statement: The study was reviewed and approved for publication by the Institutional Review Board of the Shanghai Public Health Clinical Center.
Informed consent statement: The requirement for individual written informed consent was waived since the study was retrospective in design, all patient information was anonymous and only currently existing data was used.
Conflict-of-interest statement: All the authors declare no conflict of interest related to the manuscript.
Data sharing statement: The original anonymized dataset is available upon request from the corresponding author at:
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:
Correspondence to: Liang Chen, Professor, Wenzhou Medical University, Ouhai District, Wenzhou 325000, Zhejiang Province, China.
Telephone: +86-21-379903338357 Fax: +86-21-379903335273
Received: September 20, 2016
Peer-review started: September 21, 2016
First decision: October 20, 2016
Revised: November 1, 2016
Accepted: November 16, 2016
Article in press: November 16, 2016
Published online: December 21, 2016

To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV).


This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.


The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal.


CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.

Keywords: Cirrhosis, Co-infections, Liver failure, Liver decompensation, Stages of hepatitis B virus infection

Core tip: To determine whether status of chronic hepatitis B (CHB) affects clinical outcomes of hepatitis E virus (HEV) super-infections, we investigated immunological phases, hepatitis B virus (HBV) serum markers, HBV viral load and anti-viral treatments among 228 patients with HBV-HEV co-infection. Well-compensated patients were majorly affected by HEV super-infections, and hepatitis B e antigen-negative CHB patients had the worst clinical outcomes among non-cirrhotics. Lack of proper anti-HBV treatment may contribute to the worse outcomes. These data may help to facilitate development of vaccination programs that precisely target populations at risk of poor outcome from HBV-HEV co-infections.