Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

World J Gastroenterol. 2019 Sep 7;25(33):4933-4944. doi: 10.3748/wjg.v25.i33.4933.

Abstract

Background: Proton pump inhibitors (PPIs) are widely prescribed, often without clear indications. There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients. Furthermore, PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.

Aim: To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.

Methods: Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017. PPI users were defined as cumulative defined daily dose (cDDD) ≥ 28 within a landmark period, after hospitalisation for hepatic decompensation. Cox regression analysis for comparison was done after propensity score adjustment. Further risk of hepatic decompensation was analysed by Poisson regression.

Results: Among 295 decompensated cirrhosis patients, 238 were PPI users and 57 were non-users. PPI users had higher mortality compared to non-users [adjusted HR = 2.10, (1.20-3.67); P = 0.009]. Longer PPI use with cDDD > 90 was associated with higher mortality, compared to non-users [aHR = 2.27, (1.10-5.14); P = 0.038]. PPI users had a higher incidence of hospitalization for hepatic decompensation [aRR = 1.61, (1.30-2.11); P < 0.001].

Conclusion: PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation. Longer PPI exposure with cDDD > 90 increases the risk of mortality.

Keywords: Ascites; Complications; Hepatic encephalopathy; Hospitalisation; Liver cirrhosis; Mortality; Portal hypertension; Proton pump inhibitor; Spontaneous bacterial peritonitis; Variceal bleeding.

MeSH terms

  • Acute-On-Chronic Liver Failure / epidemiology*
  • Acute-On-Chronic Liver Failure / etiology
  • Acute-On-Chronic Liver Failure / therapy
  • Aged
  • Bacterial Infections / epidemiology*
  • Bacterial Infections / etiology
  • Bacterial Infections / therapy
  • Disease Progression
  • Female
  • Hepatic Encephalopathy / epidemiology*
  • Hepatic Encephalopathy / etiology
  • Hepatic Encephalopathy / therapy
  • Humans
  • Incidence
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / mortality*
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Patient Admission / statistics & numerical data
  • Peritonitis / epidemiology*
  • Peritonitis / etiology
  • Peritonitis / therapy
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Time Factors

Substances

  • Proton Pump Inhibitors