Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites.

Mattias Mandorfer,Simona Bota,Arnulf Ferlitsch,Wolfgang Sieghart,Alexander Blacky,Thomas Reiberger,Christian Summereder,Michael Trauner,Michael Hagmann,Theresa Bucsics,Nikolaus Pfisterer,Markus Peck-Radosavljevic,Philipp Schwabl,Erica Villa

doi:10.1371/journal.pone.0110503

Mattias Mandorfer, Simona Bota + Show 12 more

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https://doi.org/10.1371/journal.pone.0110503

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Abstract

Background and AimThe aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites.Patients and MethodsWe performed a retrospective analysis of follow-up data from 607 consecutive patients with cirrhosis undergoing their first paracentesis at a tertiary center. A binary logistic regression model investigating the association between PPI intake and SBP at the first paracentesis was calculated. Competing risk analyses and Cox models were used to investigate the effect of PPIs on the cumulative incidence of SBP or other infections and transplant-free survival, respectively. Adjustments were made for age, hepatocellular carcinoma, history of variceal bleeding, varices and model of end-stage liver disease score.ResultsEighty-six percent of patients were receiving PPIs. After adjusting for potential confounding factors, PPI intake was neither associated with increased SBP prevalence at the first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6–2.06; P = 0.731) nor cumulative incidence of SBP (subdistribution hazard ratio (SHR): 1.38; 95%CI:0.63–3.01; P = 0.42) and SBP or other infections (SHR:1.71; 95%CI:0.85–3.44; P = 0.13) during follow-up. Moreover, PPI intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95%CI:0.719–1.317; P = 0.859) as well as in the subgroups of patients without SBP (HR:1.01,95%CI:0.72–1.42; P = 0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668–1.334; P = 0.742).ConclusionsThe proportion of cirrhotic patients with PPI intake was higher than in previous reports, suggesting that PPI indications were interpreted liberally. In our cohort with a particularly high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality. Thus, the severity of liver disease and other factors, rather than PPI treatment per se may predispose for infectious complications.

Highlights

Cirrhosis, which accounts for 1.8% of all deaths in Europe [1], is the 12th leading cause of death in the United States, though a recent report suggests even this rank to be an underestimation [2].According to a prognostic model proposed by D9Amico and coworkers [3], the occurrence of varices initiates the second stage of cirrhosis, the third stage is defined by the development of ascites and variceal hemorrhage initiates the fourth stage
pump inhibitor (PPI) intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95% confidence interval (95%CI):0.719–1.317; P = 0.859) as well as in the subgroups of patients without spontaneous bacterial peritonitis (SBP) (HR:1.01,95%CI:0.72–1.42; P = 0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668–1.334; P = 0.742)
In our cohort with a high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality

Summary

Introduction

Cirrhosis, which accounts for 1.8% of all deaths in Europe [1], is the 12th leading cause of death in the United States, though a recent report suggests even this rank to be an underestimation [2].According to a prognostic model proposed by D9Amico and coworkers [3], the occurrence of varices initiates the second stage of cirrhosis, the third stage is defined by the development of ascites and variceal hemorrhage initiates the fourth stage. Thirty percent of patients die within 1 month and another 30% die during the first year after onset of infection [4] These bacterial infections predominately occur in decompensated patients with advanced cirrhosis who typically have ascites. Impaired small intestinal motility [8], portal hypertension [10] and acid-suppressive therapy, such as proton pump inhibitors (PPIs) [11], have been reported as factors contributing to SIBO in patients with cirrhosis. The aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites

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