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Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients
Open Access Articles
  • Matthew J. Fasullo, University of Massachusetts Medical School
  • Prashanth Rau, University of Massachusetts Medical School
  • Dong-Qi Liu, University of Massachusetts Medical School
  • Erik Holzwanger, University of Massachusetts Medical School
  • Jomol Mathew, University of Massachusetts Medical School
  • Yurima Guilarte-Walker, University of Massachusetts Medical School
  • Gyongyi Szabo, University of Massachusetts Medical School
UMMS Affiliation
Department of Medicine, Division of Gastroenterology; Department of Population and Quantitative Health Sciences; Information Technology, Department of Data Sciences and Technology
Publication Date
Document Type

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.

  • Cirrhosis,
  • Hepatic encephalopathy,
  • Hepatology,
  • Proton pump inhibitor,
  • Proton pump inhibitors
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Copyright ©The Author(s) 2019. 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:
DOI of Published Version

World J Hepatol. 2019 Jun 27;11(6):522-530. doi: 10.4254/wjh.v11.i6.522. Link to article on publisher's site

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Creative Commons Attribution-Noncommercial 4.0
Citation Information
Matthew J. Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, et al.. "Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients" Vol. 11 Iss. 6 (2019) ISSN: 1948-5182 (Print)
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