Proton Pump Inhibitor Use and Risk of Hepatic Encephalopathy in Cirrhotic Patients: A Systematic Review and Meta-analysis

Abstract

Background: Hepatic encephalopathy (HE) is a debilitating complication of liver cirrhosis, characterized by neuropsychiatric symptoms ranging from mild cognitive impairment to coma. Proton pump inhibitors (PPIs) are widely used in cirrhotic patients for managing gastrointestinal conditions. However, emerging evidence has suggested a potential link between PPI use and HE, possibly due to increased intestinal permeability and bacterial translocation.

Objective: To evaluate and synthesize current evidence on the association between PPI use and the risk of hepatic encephalopathy in patients with liver cirrhosis through a systematic review and meta-analysis.

Methods: A total of 22 studies were included in this systematic review and meta-analysis, comprising both case-control and cohort designs. Hazard ratios (HRs) and odds ratios (ORs) were used to quantify the association between PPI use and the development of HE.

Results: The initial pooled analysis showed that PPI use was associated with an increased risk of HE, with a hazard ratio (HR) of 1.59 (95 % CI: 1.42-1.77) and an odds ratio (OR) of 2.07 (95 % CI: 1.57-2.72; I² = 96.4 %, p < 0.0001). In the OR group, a subgroup analysis by study type showed: Case-control studies: OR = 2.29 (95 % CI: 1.46-3.59, I² = 76.9 %, p < 0.0017). Retrospective cohort studies: OR = 1.107 (95 % CI: 1.05-1.166, I² = 0 %, p = 0.97). Nardelli et al. and Sun et al. were not pooled as they were prospective cohort studies. In the HR group, all included studies were retrospective cohort studies, so no further subgroup analysis was performed. After excluding high-risk studies/abstracts, the pooled HR was 1.49 (95 % CI: 1.266-1.743, I² = 37.9 %, p = 0.153).

Conclusion: This meta-analysis supports a potential association between PPI use and an increased risk of hepatic encephalopathy in cirrhotic patients. These findings underscore the importance of cautious and judicious use of PPIs in this vulnerable population, reserving them for clear clinical indications.

Keywords: Gut microbiota; Hepatic encephalopathy; Liver cirrhosis; Proton pump inhibitors.