Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis

Abstract

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in patients with cirrhosis. Proton pump inhibitors (PPIs) can contribute to small‐bowel bacterial overgrowth, but no study has investigated the link between PPIs and MHE. We investigated the relationship between MHE and PPI use as well as the role of PPI use in the development of overt HE and survival. Consecutive patients with cirrhosis (n = 310) were included in the study and followed up for 14.1 ± 12.3 months. At entry, MHE was diagnosed when the Psychometric Hepatic Encephalopathy Score was ≤–4. Data were analyzed by logistic regression for the factors associated with MHE and by time‐related models for overt HE development and survival. At inclusion, 131 out of 310 patients with cirrhosis (42%) were affected by MHE. One hundred and twenty‐five patients (40%) were using PPIs. The variables independently associated with the presence of MHE were PPI use, previous overt HE, low albumin, low sodium, and age. During follow‐up, the development of overt HE was higher (64% versus 25%, P < 0.001) and overall survival lower (41% versus 81%, P < 0.001) in PPI users than in nonusers. Variables independently associated with the development of overt HE were PPIs, history of overt HE, low albumin, MHE, and age, while variables independently associated with mortality were PPIs, development of overt HE, Model for End‐Stage Liver Disease score, low sodium, and age. Conclusion: The study identifies a potentially removable factor associated with the presence of MHE and related to the development of overt HE and survival in patients with liver cirrhosis.

Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis

“…PPIs are widely used in cirrhotic patients and are associated with poor outcomes, in part due to infections and HE. 72 PPI use can be associated with increased relative abundance of oral-origin microbiota in the distal gut after as little as 14 days of omeprazole in healthy individuals and in patients with compensated and decompensated cirrhosis. 73 These have functional consequences with ureaseproducing Streptococcaceae and higher trimethylamine N-oxide (TMAO) generation.…”

Predicting Overt Hepatic Encephalopathy for the Population With Cirrhosis

“…Given mounting interest in sarcopenia as a general risk biomarker in cirrhosis, such studies are likely highly feasible by collecting data on new HE (and other decompensations) in addition to conventional outcomes such as transplant‐free survival. Medication burden is also associated with the development of HE. Previous studies have implicated proton pump inhibitors, benzodiazepines, and nonselective betablockers . Whether these findings causally related or correlated is debatable.…”

Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: a population‐based study

“…These findings underline the potential over prescription of this class of drugs and at least half of the patients in these studies seem to have no indication for a long‐term PPI therapy 11 . Additionally, emerging evidence points towards an association of PPI use with infections as well as the development of hepatic encephalopathy in patients with cirrhosis 11,15,16 …”

“…This is mostly explained by impaired visuomotor coordination, reaction time, psychomotor speed and attention 25 . A recent study by Nardelli et al demonstrated that PPI use may increase the prevalence of minimal hepatic encephalopathy and the incidence of overt hepatic encephalopathy 16 . Therefore, it seems possible that PPI use may result in a higher frequency of falls, explanatory of increased risk of fractures.…”