Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2020; 26(6): 645-656
Published online Feb 14, 2020. doi: 10.3748/wjg.v26.i6.645
Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study
Zhu-Jun Cao, Yu-Han Liu, Chuan-Wu Zhu, Shan Yin, Wei-Jing Wang, Wei-Liang Tang, Gang-De Zhao, Yu-Min Xu, Lu Chen, Tian-Hui Zhou, Ming-Hao Cai, Hui Wang, Wei Cai, Shi-San Bao, Hai Li, Qing Xie
Zhu-Jun Cao, Yu-Han Liu, Wei-Jing Wang, Wei-Liang Tang, Gang-De Zhao, Yu-Min Xu, Lu Chen, Tian-Hui Zhou, Ming-Hao Cai, Hui Wang, Wei Cai, Qing Xie, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Chuan-Wu Zhu, Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Shan Yin, Hai Li, Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Wei-Jing Wang, Gang-De Zhao, Qing Xie, Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
Shi-San Bao, Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
Author contributions: Cao ZJ, Liu YH, and Zhu CW contributed equally to this work; Bao SS, Li H, and Xie Q contributed equally to this work; Xie Q, Li H, Cao ZJ, and Bao SS generated the concept and design of the study; Cao ZJ, Liu YH, Zhu CW, Yin S, Wang WJ, Tang WL, Zhao GD, Xu YM, Chen L, Zhou TH, Cai MH, Wang H, and Cai W collected the data; Cao ZJ and Liu YH performed statistical analysis and generated the results; Xie Q, Li H, Zhu CW, Bao SS, and Liu YH interpreted the results; Cao ZJ drafted the manuscript which was revised by all authors for important intellectual content; Xie Q was responsible for administrative, technical, or material support and study supervision. All authors have access to the data, approved this final version of the manuscript, and are accountable for all aspects of the work.
Supported by the National Natural Science Foundation of China, No. 81570535 and No. 81770587; Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period, No. 2017ZX10203201-008, No. 2018ZX09206005-003, and 2017ZX10202202-005-004; the Shanghai Three-Year Plan of the Clinical Skills and Innovations, No. 16CR1002A; the Shanghai Municipal Key Clinical Specialty, No. shslczdzk01103; the Shanghai Three-Year Plan of the Key Subjects Construction in Public Health-Infectious Diseases and Pathogenic Microorganism, No. 15GWZK0102; the Suzhou Expert Team of Clinical Medicine, No. SZYJTD201717; the Joint Research Initiative-Shanghai Jiao Tong University School of Medicine, No. YW20190002.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki. Protocol was reviewed and approved with a waiver of written informed consent by the Institutional Ethics Review Committees of Ruijin Hospital and Renji Hospital.
Informed consent statement: Oral informed consent was obtained from all patients and/or their relatives about usage of their clinical data.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: To ensure that data confidentiality is not compromised, the dataset supporting the results of this article will not be integrated in the manuscript. The datasets are available from the corresponding author on reasonable request
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Qing Xie, MD, PhD, Chief Physician, Professor, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 36 Building, No. 197, Ruijin 2nd Road, Shanghai 200025, China.
Received: November 21, 2019
Peer-review started: November 25, 2019
First decision: December 23, 2019
Revised: January 8, 2020
Accepted: January 15, 2020
Article in press: January 15, 2020
Published online: February 14, 2020
Research background

Most deaths from hepatitis B virus (HBV) infection are related to complications of cirrhosis, among which bacterial infection (BI) frequently develops in decompensated cirrhosis (DC) as reported in Western countries where alcoholic cirrhosis is frequent.

Research motivation

Investigation on BI in patients with HBV-DC would be particularly important in improving the current management of HBV-DC and acute-on-chronic liver failure (ACLF), especially in Asian countries where health care resources are relatively limited and access to liver transplantation is much more restricted.

Research objectives

To investigate the impact of BI on the outcomes of patients with HBV-DC admitted into the hospital with or without ACLF.

Research methods

This retrospective study included the patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event.

Research results

A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001)] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82).

Research conclusions

BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.

Research perspectives

It is imperative to minimize/prevent the risk of BI, as this has a negative impact on patient survival, extending well into the post-discharge period. Once BI is suspected, proper antibiotic treatment should be initiated early to prevent adverse outcomes.