The possible association of proton pump inhibitor use with acute cholangitis in patients with choledocholithiasis: a multi-center study

Background: Gallstone disease is common worldwide and can lead to severe complications, including cholangitis; thus, it is important to identify modifiable risk factors for cholangitis. Proton pump inhibitors (PPIs) are commonly prescribed to treat gastroenterological disorders. We aimed to explore whether PPI use is associated with an increased risk of acute cholangitis in patients with gallstone disease. Methods: This retrospective multicenter study included all patients arriving to the hospital over a 10-year period with various presentations of choledocholithiasis. We compared active PPI use in two groups: those with cholangitis (group A) vs. without cholangitis (group B). Results: Overall, 811 patients were included, 161 in group A and 650 in group B. The average age ± standard deviation (SD) in groups A and B was 74.5 ± 20.6 vs. 61.6 ± 20.9 years, respectively. PPI use in group A was higher vs. group B (42.9% vs. 29.1%, p = 0.001). On univariate analysis, male gender (OR 1.47, 95% confidence interval (CI) 1.04–2.08), age (OR 1.04, 95% CI 1.03–1.05), ischemic heart disease (IHD) (OR 1.68, 95% CI 1.07–2.64), hyperlipidemia (OR 1.59, 95% CI 1.11–2.29), hypertension (OR 1.81, 95% CI 1.28–2.57) and PPI use (OR 1.83, 95% CI 1.28–2.61), all were associated with acute cholangitis. On multivariate analysis, only PPI use kept its association after adjustment for age (OR 1.64, 95% CI 1.2–3.7). Conclusions: Active PPI use was associated with a higher rate of cholangitis among patients with choledocholithiasis. We advocate considering this risk before prescribing PPIs to patients with gallstones. Trial registration number: NHR-0263-20 received on 14/01/2021 date ‘retrospectively registered’.