Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis
Loai Dahabra, Malek Kreidieh, Mohammad Abureesh, Ahmad Abou Yassine, Liliane Deeb
Gastroenterology Research, doi:10.14740/gr1545
Background: Since their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not.
Methods: A retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home.
Results: In our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 -4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance.
Conclusions: Our retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients..
Financial Disclosure The authors declare no grants or financial support for the research, authorship, and publication of this article.
Conflict of Interest The authors declare that they have no competing interests.
Author Contributions LD, MA, and AAY carried out the study design, data entry, and statistical analysis. MK and LD carried out the drafting of the manuscript and its critical revision.
Abbreviations CI: confidence interval; GERD: gastroesophageal reflux disease; HLA: human leukocyte antigen; H2RA: histamine-2 receptor antagonist; ICD: International Classification of Diseases; MELD-Na: model for end-stage liver disease sodium; NSAID: non-steroidal anti-inflammatory drug; PMN: polymorphonuclear leukocyte; PPIs: proton pump inhibitors; PUD: peptic ulcer disease; RCTs: randomized clinical trials; SBP: spontaneous bacterial peritonitis; SIBO: small intestinal bacterial overgrowth; SNOMED-CT: Systematized Nomenclature of Medicine-Clinical Terms; SPSS: Statistical Package for Social Sciences
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