title: Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites.
abstract: 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).
  
  
  
  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).
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. gitdam@rm.dk.
authors.forename: Gitte
authors.initials: G
authors.lastname: Dam
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: Sanofi Aventis R&D, Paris, France.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watson
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Jepsen
mesh_terms: D000368:Aged; D001201:Ascites / Q000150:complications / Q000188:drug therapy; D001424:Bacterial Infections / Q000139:chemically induced*; D005260:Female; D006501:Hepatic Encephalopathy / Q000139:chemically induced*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D010538:Peritonitis / Q000139:chemically induced* / Q000382:microbiology*; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D054328:Proton Pump Inhibitors