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. 2024 Apr 26;6(8):101104.
doi: 10.1016/j.jhepr.2024.101104. eCollection 2024 Aug.

Proton pump inhibitor use and risk of hepatic encephalopathy: A multicentre study

Simon Johannes Gairing  1   2 , Chiara Mangini  3 , Lisa Zarantonello  3 , Elise Jonasson  4 , Henrike Dobbermann  5 , Philippe Sultanik  6 , Peter Robert Galle  1   2 , Joachim Labenz  7 , Dominique Thabut  6 , Jens Uwe Marquardt  5 , Patricia P Bloom  8 , Mette Munk Lauridsen  4 , Sara Montagnese  3   9 , Christian Labenz  1   2
Affiliations

Proton pump inhibitor use and risk of hepatic encephalopathy: A multicentre study

Simon Johannes Gairing et al. JHEP Rep. .

Abstract

Background & aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE).

Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation.

Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication.

Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication.

Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

Keywords: Acid suppression; Covert hepatic encephalopathy; Decompensated cirrhosis; Psychometric hepatic encephalopathy score.

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Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Cumulative incidence of overt HE (OHE). A three-state model was built with death and LTX as competing events. Differences between groups were calculated with Gray’s test. Cumulative OHE incidence in patients with vs without PPI use in (A) all patients (p = 0.13), (B) patients with Child-Pugh A (p = 0.5), (C) patients with Child-Pugh B (p = 0.3), and (D) patients without a history of OHE (p = 0.082). Abbr.: PPI, proton pump inhibitor.
Fig. 2
Fig. 2
Cumulative incidence of overt HE (OHE). Cumulative OHE incidence in (A) patients with vs without an indication for PPI use (p = 0.6), (B) patients with an indication for PPI use and those without PPI use (p = 0.5), (C) patients with PPI use but no indication and those without PPI use (p = 0.1). Abbr.: PPI, proton pump inhibitor.
See this image and copyright information in PMC

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