Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2683-2698
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2683
Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis
Xin-Xing Tantai, Long-Bao Yang, Zhong-Cao Wei, Cai-Lan Xiao, Li-Rong Chen, Jin-Hai Wang, Na Liu
Xin-Xing Tantai, Long-Bao Yang, Zhong-Cao Wei, Cai-Lan Xiao, Li-Rong Chen, Jin-Hai Wang, Na Liu, Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Author contributions: Tantai XX, Wang JH, and Liu N contributed to the study concept and design; Yang LB and Wei ZC contributed to the acquisition of data; Tantai XX, Wang JH, Liu N, Xiao CL, and Chen LR contributed to the analysis and interpretation of data; Tantai XX contributed to the statistical analysis; Tantai XX drafted the manuscript; Wang JH and Liu N contributed to the critical revision of the manuscript for important intellectual content, and study supervision.
Conflict-of-interest statement: The authors have no potential conflicts of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Na Liu, PhD, Doctor, Division of Gastroenterology, The Second Affiliated Hospital, Xi’an Jiaotong University, No. 157, Xiwu Road, Xi’an, Shaanxi Province, China. liunafmmu@163.com
Telephone: +86-29-8767-9335 Fax: +86-29-8767-9368
Received: March 12, 2019
Peer-review started: March 13, 2019
First decision: April 11, 2019
Revised: April 21, 2019
Accepted: May 3, 2019
Article in press: May 3, 2019
Published online: June 7, 2019
Processing time: 87 Days and 5.7 Hours
ARTICLE HIGHLIGHTS
Research background

Given their safety profile, proton pump inhibitors (PPIs) are commonly prescribed for patients with advanced liver disease. Recent studies have reported that using PPIs may increase the risk of hepatic encephalopathy (HE) by increasing the gastric pH and bacterial translocation and changing intestinal flora. About the association between PPI use and HE, evidence-based conclusions need to be drawn.

Research motivation

PPIs are often overused in patients with advanced liver disease. Systematically reviewing the existing evidence on the association between PPI use and the risk of HE could help regulate clinical practice.

Research objectives

The aim of this meta-analysis was to analyze data on the association between PPI use and the risk of HE in patients with advanced liver disease.

Research methods

Electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched for relevant articles meeting the inclusion criteria. We conducted a meta-analysis of all comparative studies that evaluated the association between PPI use and the risk of HE. The primary outcome was pooled risk estimates of HE in the PPI group and non-PPI groups. Subgroup analyses by different clinical and methodological characteristics were also performed.

Research results

We finally included nine observational studies (five case-control studies and four cohort studies). This analysis showed that PPI use was associated with an increased risk of developing HE regardless of the study design. The sensitivity analysis excluding conference abstracts or focusing on patients without prior HE showed a similar result. The results of subgroup analyses suggested that the heterogeneity may come from different study designs and definitions of PPI use.

Research conclusions

Compared with the non-PPI group, the PPI group has an elevated risk of HE in patients with advanced liver disease. This finding reminds clinicians that they should strictly adhere to the indications for PPI treatment in patients with advanced liver disease.

Research perspectives

To further explore the association between PPI therapy and the risk of HE, future studies need to refine the impact of the PPI types, time of PPI administration, and method of PPI administration on HE. In addition, more high-quality prospective studies and mechanistic studies are required to better understand the association between PPI use and the risk of HE.