Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2675-2682
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2675
Proton pump inhibitor use increases hepatic encephalopathy risk: A systematic review and meta-analysis
Yun-Jie Ma, Zong-Xun Cao, Yong Li, Shun-Yi Feng
Yun-Jie Ma, Zong-Xun Cao, Yong Li, Shun-Yi Feng, Emergency Department, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
Author contributions: Ma YJ and Cao ZX contributed to conception and design of the study; Ma YJ, Cao ZX, and Feng SY contributed to acquisition of data; Cao ZX, Li Y, and Feng SY analyzed and interpreted the data; Ma YJ drafted the article; Li Y critically revised the manuscript; all authors approved the final version to be published.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: This systematic review was performed in accordance with the standards set forth by the statement from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
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:
Corresponding author: Yong Li, MD, Chief Doctor, Emergency Department, Cangzhou Central Hospital, No. 16, Xinhua Road, Yunhe Qu, Cangzhou 061000, Hebei Province, China.
Telephone: +86-13333367871 Fax: +86-0317-2075685
Received: March 21, 2019
Peer-review started: March 21, 2019
First decision: April 4, 2019
Revised: April 24, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: June 7, 2019
Research background

Proton pump inhibitors (PPIs) are the first choice of treatment for esophagitis and peptic ulcer disease, as well as the prevention of nonsteroidal anti-inflammatory drug associated ulcers, Zollinger-Ellison syndrome, and functional dyspepsia. In acid-related diseases, the benefits of PPI use outweigh their potential harm. Unfortunately, the negative effects of PPI use are generally underestimated due to marketing strategy and neglected reporting bias in published trials. Thus, not all PPIs are used following evidence-based guidelines in the clinical setting, and PPIs are overprescribed in both inpatient and outpatient settings.

Research motivation

Regarding concerns over liver adverse effects, a previous meta-analysis showed that PPIs increase the risk of hepatic encephalopathy (HE) in patients with hepatic failure. However, the results are restricted because of the inclusion of a relatively small number of studies. New primary studies have also been recently published, and their results are controversial.

Research objectives

In this meta-analysis, we aimed to update, compile, and critically review the existing evidence on the risk of HE in patients with liver cirrhosis and PPI use and provide a quantitative estimate of the relationship between PPI use and HE risk.

Research methods

A systematic search on PubMed, Web of Science, EMBase, and ScienceDirect databases was conducted up to December 31, 2018 for eligible studies involving PPI use and HE risk. The odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model. Publication bias was evaluated using the Begg’s, Egger’s tests, and trim-and-fill method.

Research results

The findings from this study indicated an increase of 50% risk of HE among PPI users, which is consistent with the results obtained in a previous study.

Research conclusions

Our meta-analysis expanded the results of previous studies and increased the statistical power to evaluate the effects.

Research perspectives

Randomized multicentric studies with a large sample size should be conducted to provide further insight into the potential impact of PPIs on HE.