title: Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis.
abstract: BACKGROUND
  There is increasing evidence that proton pump inhibitors (PPIs) increase the rate of infections in patients with decompensated cirrhosis.
  
  
  OBJECTIVE
  To estimate the extent to which proton pump inhibitors (PPIs) increase the rate of infections among patients with decompensated cirrhosis.
  
  
  METHODS
  We conducted a retrospective propensity-matched new user design using US Veterans Health Administration data. Only decompensated cirrhotic patients from 2001 to 2009 were included. New PPI users after decompensation (n = 1268) were 1:1 matched to those who did not initiate gastric acid suppression. Serious infections, defined as infections associated with a hospitalisation, were the outcomes. These were separated into acid suppression-related (SBP, bacteremia, Clostridium difficile and pneumonia) and non-acid suppression-related. Time-varying Cox models were used to estimate adjusted hazard ratios (HR) and 95% CIs of serious infections. Parallel analyses were conducted with H2 receptor antagonists (H2RA).
  
  
  RESULTS
  More than half of persons with decompensated cirrhosis were new users of gastric acid suppressants, with most using PPIs (45.6%) compared with H2RAs (5.9%). In the PPI propensity-matched analysis, 25.3% developed serious infections and 25.9% developed serious infections in the H2RA analysis. PPI users developed serious infections faster than nongastric acid suppression users (adjusted HR: 1.66; 95% CI: 1.31–2.12). For acid suppression-related serious infections, PPI users developed the outcome at a rate 1.75 times faster than non-users (95% CI: 1.32–2.34). The H2RA findings were not statistically significant (HR serious infections: 1.59; 95% CI: 0.80–3.18; HR acid suppression-related infections: 0.92; 95% CI: 0.31–2.73).
  
  
  CONCLUSIONS
  Among patients with decompensated cirrhosis, proton pump inhibitors but not H2 receptor antagonists increase the rate of serious infections.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, VA, USA. jsbajaj@vcu.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Bajaj
authors.forename: S M
authors.initials: SM
authors.lastname: Ratliff
authors.forename: D M
authors.initials: DM
authors.lastname: Heuman
authors.forename: K L
authors.initials: KL
authors.lastname: Lapane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000139:chemically induced*; D003015:Clostridium Infections / Q000139:chemically induced*; D005260:Female; D005744:Gastric Acid; D006635:Histamine H2 Antagonists / Q000009:adverse effects; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States; D014728:Veterans / Q000706:statistics & numerical data
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors