Background: Microscopic colitis (MC) is an inflammatory condition of the colon, characterized by watery, non-bloody, diarrhoea. There is a known overlap between MC and bile-salt malabsorption and patients with MC have been found to have decreased levels of fibroblast growth factor 19 (FGF-19), a key regulator of the enterohepatic circulation in that FGF-19 inhibition leads to an increased production of bile in the liver. Moreover, individuals who have undergone a cholecystectomy may have an impaired emulsification of dietary lipids, leading to decreased fat absorption and elevated colonic fat concentrations, often resulting in diarrhoea. Hence, we hypothesized an association between cholecystectomy and subsequent development of MC. To address this unexplored relationship, we aimed to investigate whether cholecystectomy is a risk factor for MC.

Methods: Using data from the nationwide histopathology database ESPRESSO, we conducted a matched case control study in Sweden. A total of 12,853 patients with biopsy confirmed MC between 2002 and 2017 were identified and matched to 61,532 controls from the general population. To address intrafamilial confounding, we also identified 13,449 full siblings (to patients with MC). Cholecystectomy was defined by procedure codes (JKA20-21) and as the altered bile-flow caused by a cholecystectomy likely manifests its effect in the near term, only cholecystectomies in the last five years preceding MC diagnosis/matching date were taken into consideration. Open and laparoscopic cholecystectomy were separately examined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for prior cholecystectomy were computed using conditional logistic regression.

Results: Some 72% of patients with MC were female and the median age at MC diagnosis was 63.6 years (interquartile range (IQR)=51.0--73.3). Among patients with MC, 182 (1.4%) had a record of prior cholecystectomy and the corresponding number for controls was 383 (0.6%), yielding an adjusted odds ratio of 2.25 (95% CI=1.88-2.69). The aOR for open and laparoscopic cholecystectomy was 2.02 (95%CI=1.30-3.12) and 2.32 (95%CI=1.91-2.81), respectively (Figure 1). To address surveillance bias, we conducted a sensitivity excluding individuals within one year of cholecystectomy, with only a minor effect on our point estimate, aOR 2.17 (95%CI=1.78-2.65). When using siblings as controls our estimate attenuated but remained statistically significant (aOR 1.48; 95%CI=1.14-1.96).

Conclusion: Patients who undergo cholecystectomy are at a 2.3-fold increased risk of being diagnosed with MC within five years. The findings underline that MC should be considered as a differential diagnosis in patients with a history of cholecystectomy presenting with diarrhoea. Finally, our observations motivate further studies into the mechanisms involved, especially with regards to bile flow.

Bjorn Lindkvist

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