History of Cholecystectomy and Risk of Clostridium Difficile Infection

Cholecystectomy affects bile acid physiology. There is growing evidence that both primary and secondary bile acids play a role in the pathogenesis of Clostridium difficile infections (CDIs).

The aim of this study is to elucidate the relationship and risk of CDI in patients with cholecystectomy.

We performed a matched cohort study of patients in an integrated healthcare system in Northern California from January 2000 to December 2018. Patients with cholecystectomy (cases, n = 12,617) identified based on Current Procedure Terminology codes were age- and sex-matched to patients without cholecystectomy (controls, n = 37,851). We excluded those with history of CDI at baseline and calculated the hazard ratio (HR) for development of CDI after adjusting for confounders.

We found total of 351 incident CDI during average of 4.66 years of follow-up among cases and controls. In multivariate analysis, cholecystectomy was associated with elevated risk of CDI (HR 1.53, 95% confidence interval 1.14-2.04) compared with controls. Stratified analysis shows this effect does not differ according use of proton pump inhibitors (P_interaction = 0.142), antibiotics (P_interaction = 0.387), and hospitalization (P_interaction = 0.252).

Cholecystectomy is associated with mild increased risk of incident CDI, but this effect is not influenced by use of proton pump inhibitors, antibiotics, or hospitalization. Future prospective studies should be conducted to validate these findings and evaluate bile acid changes after a cholecystectomy.