Proton pump inhibitor use and risk of hepatic encephalopathy: A multicentre study
Simon Johannes Gairing,
Chiara Mangini,
Lisa Zarantonello,
Elise Jonasson,
Henrike Dobbermann,
Philippe Sultanik,
Peter Robert Galle,
Joachim Labenz,
Dominique Thabut,
Jens Uwe Marquardt,
Patricia P. Bloom,
Mette Munk Lauridsen,
Sara Montagnese,
Christian Labenz
Affiliations
Simon Johannes Gairing
Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
Chiara Mangini
Department of Medicine, University of Padova, Padova, Italy
Lisa Zarantonello
Department of Medicine, University of Padova, Padova, Italy
Elise Jonasson
Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
Henrike Dobbermann
Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
Philippe Sultanik
Service d'hépato-gastroentérologie, Sorbonne Université, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Paris, France
Peter Robert Galle
Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
Joachim Labenz
Department of Medicine, Diakonie Hospital Jung-Stilling, Siegen, Germany
Dominique Thabut
Service d'hépato-gastroentérologie, Sorbonne Université, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Paris, France
Jens Uwe Marquardt
Department of Medicine I, University Hospital Schleswig-Holstein, Lübeck, Germany
Patricia P. Bloom
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, United States
Mette Munk Lauridsen
Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Esbjerg, Denmark
Sara Montagnese
Department of Medicine, University of Padova, Padova, Italy; Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
Christian Labenz
Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany; Corresponding author. Address: Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany; Tel.: +49 (0) 6131 17 2380, fax: +49 (0) 6131 17 477282.
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.
