Proton pump inhibitor use increases hepatic encephalopathy risk: A systematic review and meta-analysis

Abstract

BACKGROUND Several studies have been conducted to explore the association between the use of proton pump inhibitors (PPIs) and hepatic encephalopathy (HE) risk in patients with liver cirrhosis. However, their results are controversial. AIM To perform a systematic review and meta-analysis to evaluate the HE risk among PPI users. METHODS A systematic search on PubMed, Web of Science, EMBase, and ScienceDirect databases was conducted up to December 31, 2018 for eligible studies involving PPI use and HE risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Publication bias was evaluated using Begg’s test, Egger’s test, and trim-and-fill method. RESULTS Seven studies with 4574 patients were included in the present meta-analysis. The meta-analysis results indicated a significant association between the PPI use and HE risk (OR = 1.50; 95%CI: 1.25-1.75) with low heterogeneity ( I 2 = 14.2%, P = 0.321). Although publication bias existed when Egger’s tests were used ( P = 0.005), the trim-and-fill method verified the stability of the pooled result. Sensitivity analyses suggested that the results of this meta-analysis were robust. CONCLUSION The current evidence indicates that PPI use increases HE risk in patients with liver cirrhosis. Further studies with a large data set and well-designed models are needed to validate our findings.

Adverse Effects of Proton Pump Inhibitors—Evidence and Plausibility

“…PPI use increases the risk of developing HE in patients with cirrhosis [104] as well as the severity of HE [105]. Two recent meta-analyses confirmed the association [106,107] and the proposed mechanism is that PPIs induce bacterial overgrowth in the intestine [108]. It is known that PPIs do not only change the bacterial composition in the stomach, but also in faeces with a significant shift towards oral flora in principal coordinate analyses (PCoA) [109,110], demonstrating that the entire gastrointestinal tract is affected downstream of gastric hypoacidity.…”

Proton pump inhibitor use and mortality in patients with cirrhosis: a meta-analysis of cohort studies

“…Subsequently, the impaired intestinal epithelial barrier in patients with cirrhosis [44] may facilitate the translocation of the overgrown bacteria to mesenteric lymph nodes, which finally leads to SBP and other infections [45]. Moreover, PPIs may also contribute to the gut dysbiosis that generally exists in patients with cirrhosis, whereas altered gut microbiota can induce or exacerbate HE [46,47], another complication that has been related to increased mortality risk in cirrhotic patients [12]. In addition, studies in overall population showed that PPI use may be associated with increased risks of cardiovascular adverse events [48], stroke [49], and fractures [50], which may also lead to increased mortality.…”

“…However, the indications and clinical efficacy of PPIs in these patients remain to be validated, which highlights the possible overutilization of PPIs in patients with cirrhosis [5]. Subsequently, increasing evidence from epidemiological studies indicated that PPI use may be associated with adverse outcomes in cirrhotic patients, spontaneous bacterial peritonitis (SBP) [6][7][8][9][10][11], and hepatic encephalopathy (HE) [12,13]. However, it remains unknown whether PPI use affects mortality in these patients.…”

Hepatic Encephalopathy and Nutrition Influences: A Narrative Review

“…In a case‐control study in Taiwan, it was shown that PPI use increases the risk of HE development in a dose‐dependent fashion . Furthermore, a recent meta‐analysis including 7 trials with 4574 patients confirmed that PPI use increases the risk of HE development in cirrhotic patients …”