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
Abstract
BACKGROUND

Several studies have explored the association between the use of proton pump inhibitors (PPIs) and the risk of developing hepatic encephalopathy (HE) in patients with advanced liver disease. However, the evidence-based conclusions are controversial. We hypothesized that using PPIs may increase the risk of HE in patients with advanced liver disease. If confirmed, clinicians must strictly adhere to the indications for PPI treatment in this population.

AIM

To evaluate the pooled risk of HE in patients with advanced liver disease who use PPIs.

METHODS

Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from the date of database inception through January 8, 2019 to identify comparative studies evaluating the association between PPI use and the risk of HE. Data from the included studies were extracted. The random-effects model was used for pooling risk estimates and the corresponding 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also performed.

RESULTS

In total, 4342 patients from five case-control studies and 188053 patients from four cohort studies were included in this analysis. In patients with advanced liver disease, PPI use was associated with an elevated risk of developing HE, with significant heterogeneity. The pooled odds ratio for case-control studies was 2.58 (95%CI: 1.68-3.94, I2 = 72%). The pooled RR for cohort studies was 1.67 (95%CI: 1.30-2.14, I2 = 67%). The results of the subgroup analyses suggested that the heterogeneity may be the result of differences in the study designs and the definitions of PPI use. The sensitivity and subgroup analyses did not alter our findings.

CONCLUSION

In patients with advanced liver disease, PPI use is associated with an elevated risk of HE. Future large prospective studies are needed to confirm this association.

Keywords: Proton pump inhibitors; Cirrhosis; Hepatic encephalopathy; Systematic review; Meta-analysis

Core tip: Proton pump inhibitors (PPIs) are very commonly used in patients with advanced liver disease. Remarkably, previous studies have shown that approximately 50% of indications for PPIs treatment were unclear or inadequate in this special group of patients. All these may be because PPIs are generally considered safe. However, this meta-analysis shows that using PPIs is associated with an increased risk of hepatic encephalopathy (HE) in patients with advanced liver disease. This reminds clinicians that inappropriate use of PPIs may be not beneficial but put patients at an elevated risk of HE. These findings still need to be confirmed by more high-quality prospective studies because of the limitations of this meta-analysis.