Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis
Bibliographic record
Abstract
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 receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".