Abstract / Summary
Abstract Purpose To characterize the clinical presentation, disease course, and outcomes of patients with concurrent primary sclerosing cholangitis (PSC) and celiac disease (CeD), including those with concomitant inflammatory bowel disease (IBD). Methods Retrospective EHR analysis (MGB RPDR, BIDMC Celiac Center, All of Us) identified patients with confirmed PSC and CeD (ICD-10, encounter threshold > 1, validated clinically/serologically/histologically). Primary outcomes were hepatic complications and time to liver transplantation, compared against two 3:1 age-matched cohorts (PSC + IBD, n = 54; PSC-only, n = 54). Results Among 7.5 million patients in RPDR, 18,375 had CeD and 992 had PSC, with 13 observed cases of overlap versus 2.43 expected (OR 5.35, 95% CI 3.08–9.30; p < 0.001). Eighteen patients met full inclusion criteria (67% male, 94% White, mean age 47.8 years at PSC diagnosis). IBD was present in 72%, predominantly Ulcerative Colitis (56%). With high gluten-free diet adherence (89%), hepatic complications occurred in 89% of patients, with cirrhosis in 50%. Liver transplantation was required in 22%, at a mean of 5.4 years from PSC diagnosis among transplants with dated intervals, with no post-transplant PSC recurrence observed among the 4 transplanted patients. Compared with matched PSC + IBD (n = 54) and PSC-only (n = 54) control cohorts, liver transplantation was numerically more frequent in the PSC + CeD cohort than in either control cohort, though this difference did not reach significance (22.2% vs 5.6% vs 13.0%; chi-square p = 0.127). Conclusion PSC and CeD co-occur at a significantly higher frequency than expected, suggesting shared autoimmune pathogenic mechanisms. The substantial hepatic complication burden and frequent IBD co-occurrence highlight the clinical importance of this overlap and the need for multidisciplinary management and routine autoimmune screening in affected patients. Matched-cohort comparisons further suggest a numerically elevated, though not statistically significant, risk of liver transplantation in PSC + CeD patients relative to PSC + IBD patients without celiac disease, alongside a significantly elevated risk of cirrhosis and PSC–autoimmune hepatitis overlap.