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

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. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).