Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2019; 11(6): 522-530
Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.522
Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients
Matthew Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Jomol P Mathew, Yurima Guilarte-Walker, Gyongyi Szabo
Matthew Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Gyongyi Szabo, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States
Jomol P Mathew, Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA 01605, United States
Yurima Guilarte-Walker, Department of Data Sciences and Technology, Information Technology, University of Massachusetts Medical School, Worcester, MA 01605, United States
Author contributions: Fasullo M designed the study and wrote the manuscript; Rau P, Liu DQ and Holzwanger E helped edit the paper and assisted with statistical analysis; Mathew JP and Guilarte-Walker Y assisted with data collection and defining the patient population; Szabo G was the senior author, provided concepts and oversight for the study design, data acquisition, interpretation and editing of the manuscript.
Institutional review board statement: The study was reviewed and approved by the University of Massachusetts Medical School Institutional Review Board Approved Protocol (H00012102).
Informed consent statement: This study was approved by the UMMS IRB. Because this was performed as a retrospective study using data assembled from electronic health records based on waiver of consent from the IRB, individual consents were not obtained.
Conflict-of-interest statement: Gyongyi Szabo received research funding from the National Institute for Alcoholism and Alcohol Abuse, Intercept, Tobira, Signablock and Gilead. GS is a consultant for TerraFirma, Glympse, Quest Diagnostics, Allergan, Arrow Diagnostics, Salix and GLG. No other potential conflicts of interest relevant to this article were reported.
Open-Access: This 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 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: Gyongyi Szabo, MD, PhD, Professor, Department of Medicine, University of Massachusetts Medical School, 364 Planation Street, Worcester, MA 01605, United States. gyongyi.szabo@umassmed.edu
Telephone: +1-508-8565275
Received: January 16, 2019
Peer-review started: January 17, 2019
First decision: March 5, 2019
Revised: April 26, 2019
Accepted: June 17, 2019
Article in press: June 17, 2019
Published online: June 27, 2019
Abstract
BACKGROUND

Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.

AIM

To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE in patients with cirrhosis.

METHODS

This is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection, gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission.

RESULTS

The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group (P = 0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers (P = 0.046). Twenty-seven (31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group (16.7%) (P = 0.138). Finally, 10 (11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group (2.8%) (P = 0.220).

CONCLUSION

Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

Keywords: Cirrhosis, Hepatic encephalopathy, Proton pump inhibitors, Hepatology, Proton pump inhibitor

Core tip: In this study, we investigate whether proton pump inhibitor (PPI) use in hepatic encephalopathy patients predisposes them to more severe stages of hepatic encephalopathy as per West Haven Criteria. We found that chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for hepatic encephalopathy compared to patients that did not use PPIs. Our data also indicated that cirrhotic patients on PPIs have longer hospital stays, with increased morbidity and mortality during their hospital stays.