Microscopic colitis and primary sclerosing cholangitis are bidirectionally associated: A nationwide matched cohort and case-control study.

Abstract

Microscopic colitis (MC) is an inflammatory disease of the colon. Although there is a known association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), evidence linking MC and PSC remains scarce. We aimed to investigate the bidirectional association between MC and PSC. Leveraging the nationwide Swedish histopathology cohort Epidemiology Strengthened by histoPathology Reports in Sweden, we conducted a matched cohort study (2002-2023, follow-up until 2024) and a case-control study (1987-2023). Patients with IBD were excluded. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox regression and adjusted odds ratios (aORs) using conditional logistic regression. The cohort study included 21,340 patients with biopsy-confirmed MC and 101,707 matched reference individuals (matched by age, sex, birth year and county). Over a median follow-up of 7 years, PSC was diagnosed in 21 patients with MC and 15 reference individuals, corresponding to incidence rates of 11.9 (95% CI = 7.8-18.3) and 1.7 (95% CI = 1.0-2.8) per 100,000 person-years, yielding an aHR of 7.17 (95% CI = 3.69-13.9). The case-control study included 22,729 MC cases and 108,467 matched controls. Prior PSC was more frequent among MC cases (19/22,729; 0.08%) than controls (12/108,467; 0.01%), yielding an aOR of 7.26 (95% CI = 3.50-15.1). Our findings remained robust across multiple sensitivity analyses, including sibling-controlled analyses. This nationwide study reveals a bidirectional association between MC and PSC. Although absolute risks are low, these findings suggest that MC may have diagnostic relevance in suspected PSC cases, and vice versa. Physicians treating MC patients should be alert to signs and symptoms of PSC.