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United European Gastroenterol J. 2018 Oct;6(8):1179-1187. doi: 10.1177/2050640618773564. Epub 2018 Apr 23.

Association of proton pump inhibitors with the risk of hepatic encephalopathy during hospitalization for liver cirrhosis.

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Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China.
Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China.
Division of Gastroenterology, Vancouver General Hospital, Vancouver, Canada.
Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.



Hepatic encephalopathy is associated with altered gut microbiota. Proton pump inhibitors increase the risk of small bowel bacterial overgrowth.


This was a case-control study aimed at exploring the relationship of proton pump inhibitor use with the risk of hepatic encephalopathy during hospitalization in liver cirrhosis.


Case and control groups were defined as cirrhotic patients who developed hepatic encephalopathy during hospitalization and those without hepatic encephalopathy at admission or during hospitalization, respectively. Age, gender, and Child-Pugh score were matched between the groups. Odds ratios with 95% confidence intervals were calculated to express the association of proton pump inhibitors with the risk of hepatic encephalopathy. Four subgroup analyses were performed after excluding patients with acute upper gastrointestinal bleeding, infections, and in-hospital death, and after matching model for end-stage liver disease score.


In the overall analysis, 128 patients were included in each group of cases and controls. The proportion of proton pump inhibitor use was significantly higher in the case group than the control group (79.7% vs 43%, p < 0.001). Proton pump inhibitor use (odds ratio = 3.481, 95% confidence interval: 1.651-7.340, p = 0.001) was independently associated with the development of hepatic encephalopathy in the multivariate analysis. In the four subgroup analyses, proton pump inhibitor use remained independently associated with the risk of hepatic encephalopathy.


Proton pump inhibitor use might increase the risk of hepatic encephalopathy during hospitalization.


Proton pump inhibitors; gut microbiota; hepatic encephalopathy; liver cirrhosis; risk

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