Proton Pump Inhibitor Therapy and Hepatic Encephalopathy Risk in Cirrhotic Patients: A Systematic Review with Meta-analysis.

Abstract

Use of proton pump inhibitor (PPI) in patients with cirrhosis has been linked to the development of hepatic encephalopathy (HE). Little is known about the incidence rate of HE due to PPI therapy. We conducted a meta-analysis to explore the association between PPI use and the incidence of HE. We searched PubMed, EMBASE databases and The Cochrane Library from inception to March 2019 for studies describing the association between PPI exposure and incidence of HE; we identified studies that provided the adjusted estimates of odds ratio (OR)/relative ratio (RR)/hazard ratio (HR), and the pooled RRs on the incidence of HE were calculated. Summary estimates were calculated using random effects models. We analyzed data from 10 eligible studies; PPI users had an increased risk of HE compared with non-PPI user, with a pooled RR of 1.81 (95% CI 1.58-2.06), with notable heterogeneity (I2 = 85.2%, p <0.0001). In subgroup of considering the incidence of HE after yrans-jugular intrahepatic portosystemic shunt (TIPS), the pooled RR was 3.09 (95% CI 2.23-4.27), with no statistical heterogeneity (I2 = 0.0%, p = 0.484); another subgroup analysis was conducted for the complication of the enrolled patients with the status of ascites, the pooled RR was 1.39 (95% CI 1.10-1.77). The result of statistical heterogeneity was low (I2 = 46.2%, p = 0.156). We found PPI therapy increased the risk of HE in cirrhotic patients, and higher risk was found in post-operative TIPS. Additional studies are warranted to inform clinical decision making.