Association of Spontaneous Bacterial Peritonitis and Use of Proton Pump Inhibitors among Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis

Abstract

Background:
Spontaneous bacterial peritonitis (SBP) is a frequent complication seen among cirrhotic patients resulting in increased hospitalization and has an estimated 30-day mortality of 33%. While the use of proton pump inhibitors (PPI) has been associated with higher incidence of SBP, previous studies provided conflicting conclusions.

Objective:
This study aims to re-assess the association between PPI use and SBP incidence with larger, updated data. Methods: Database of Medline, Cochrane, and Google scholar were used to search for relevant articles. Two reviewers independently assessed the quality of each paper. Disagreements were resolved by the third author. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was observed and complied with. Pooled odds ratios with 95% confidence intervals were calculated. Sub-group analysis was done to decrease heterogeneity.

Results:
Twenty-two studies (eight case-control, 13 cohort, and one randomized controlled trial) involving 10,828 patients were analyzed. Results showed a statistically significant association between SBP and PPI use (pooled odds ratio (OR): 2.03, 95% CI of 1.67-2.45), with substantial heterogeneity. Subgroup analysis involving cohort and randomized controlled trial revealed statistically significant association, although weaker (OR: 1.88 with 95% CI of 1.51-2.34, p<0.00001) and has substantial heterogeneity. For case-control studies, OR is 2.64 with 95% CI of 1.91-3.64. Pooled OR for high quality studies is 1.93 with 95% CI of 1.57-2.38, p<0.00001). The funnel plot was asymmetric suggesting publication bias.

Conclusion:
This meta-analysis showed there is statistically significant association, although weak, between higher incidence of SBP and PPI use. This updated meta-analysis suggests judicious use of PPI among cirrhotic patients with ascites.