Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites

Hepatology. 2016 Oct;64(4):1265-72. doi: 10.1002/hep.28737. Epub 2016 Aug 24.


Proton pump inhibitors (PPIs) may be a risk factor for hepatic encephalopathy (HE) in patients with cirrhosis, possibly through translocation of gut bacteria, which can also lead to spontaneous bacterial peritonitis (SBP). We examined the associations between PPIs and development of HE or SBP in patients with cirrhosis with ascites. We used data from three 1-year trials of satavaptan for ascites control. We used Cox regression to compare HE and SBP rates between users and nonusers of PPIs. At inclusion, 39% of the 865 patients with cirrhosis with ascites used PPIs, 52% used them at some point during the follow-up, and the proportion of current users was always in the 30%-39% range. There were 189 first-time HE episodes during the follow-up, and the cumulative 1-year risk was 31% for those who used PPIs at baseline versus 25% for those who did not. The confounder-adjusted hazard ratio (HR) of HE for current PPI use versus current nonuse was 1.36 (95% confidence interval [CI], 1.01-1.84). The HR for overt HE was higher (adjusted HR = 1.88; 95% CI, 1.21-1.91). During the follow-up, 86 patients developed SBP. The adjusted HR of SBP for current PPI users versus nonusers was 1.72 (95% CI, 1.10-2.69).

Conclusion: PPIs were used by 52% of this international cirrhosis cohort during a 1-year period and was a risk factor for developing HE and SBP. These findings are consistent with the hypothesis that PPIs may increase translocation of gut bacteria. (Hepatology 2016;64:1265-1272).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ascites / complications
  • Ascites / drug therapy
  • Bacterial Infections / chemically induced*
  • Female
  • Hepatic Encephalopathy / chemically induced*
  • Humans
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Peritonitis / chemically induced*
  • Peritonitis / microbiology*
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Risk Factors


  • Proton Pump Inhibitors