Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2019; 25(33): 4933-4944
Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4933
Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis
Marianne Anastasia De Roza, Lim Kai, Jia Wen Kam, Yiong Huak Chan, Andrew Kwek, Tiing Leong Ang, John Chen Hsiang
Marianne Anastasia De Roza, Lim Kai, Andrew Kwek, Tiing Leong Ang, John Chen Hsiang, Department of Gastroenterology and Hepatology, Changi General Hospital, Singhealth 529889, Singapore
Jia Wen Kam, Clinical Trials and Research Unit, Changi General Hospital, Singhealth 529889, Singapore
Yiong Huak Chan, Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 160608, Singapore
Author contributions: De Roza MA and Hsiang JC designed the study and methods, and contributed to data collection, data verification, data analysis, interpretation of data, manuscript preparation, final drafting, and final approval of the version to be published; Kai L assisted with data collection and data verification; Kam JW and Chan YK performed the statistical analysis and interpretation of data; Kwek A and Ang TL contributed to the critical review of the manuscript and final approval of the version to be published.
Institutional review board statement: This study was conducted after receiving approval from the Singhealth Centralized Institutional Review Board with waiver of informed consent.
Informed consent statement: This study was approved by the Singhealth IRB for waiver of informed consent.
Conflict-of-interest statement: All authors declare there are no conflicts of interest. None of the authors received financial support or grants for this study.
Data sharing statement: Statistical coding and dataset is available from the corresponding author at
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 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: John Chen Hsiang, MBChB, Attending Doctor, Doctor, Senior Researcher, Department of Gastroenterology and Hepatology, Changi General Hospital, 2 Simei Street 3, Singhealth 529889, Singapore.
Telephone: +65-69302923
Received: March 25, 2019
Peer-review started: March 25, 2019
First decision: May 24, 2019
Revised: July 12, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 7, 2019

Proton pump inhibitors (PPIs) are widely prescribed, often without clear indications. There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients. Furthermore, PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.


To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.


Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017. PPI users were defined as cumulative defined daily dose (cDDD) ≥ 28 within a landmark period, after hospitalisation for hepatic decompensation. Cox regression analysis for comparison was done after propensity score adjustment. Further risk of hepatic decompensation was analysed by Poisson regression.


Among 295 decompensated cirrhosis patients, 238 were PPI users and 57 were non-users. PPI users had higher mortality compared to non-users [adjusted HR = 2.10, (1.20-3.67); P = 0.009]. Longer PPI use with cDDD > 90 was associated with higher mortality, compared to non-users [aHR = 2.27, (1.10-5.14); P = 0.038]. PPI users had a higher incidence of hospitalization for hepatic decompensation [aRR = 1.61, (1.30-2.11); P < 0.001].


PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation. Longer PPI exposure with cDDD > 90 increases the risk of mortality.

Keywords: Proton pump inhibitor, Liver cirrhosis, Mortality, Hospitalisation, Complications, Portal hypertension, Variceal bleeding, Ascites, Spontaneous bacterial peritonitis, Hepatic encephalopathy

Core tip: Most proton pump inhibitor (PPI) studies have issues with poorly defining PPI users and having baseline confounders. Also, studies on PPI use in liver cirrhosis have not been focused on decompensated cirrhosis. Using propensity score analysis, we adjusted for 43 variables including baseline characteristics, comorbidities, PPI indication, and medications (including antiplatelets). Landmark analysis was used to define PPI users to reduce bias. PPI use in patients with decompensated liver cirrhosis was associated with higher mortality and increased risk of hepatic decompensation requiring hospital admissions. Longer PPI exposure with > 90 defined daily doses further increased mortality risk.