Autoimmune diseases in primary sclerosing cholangitis and their first-degree relatives

Background:Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel disease (IBD). However, there is limited overlap between IBD and PSC risk genes, but a stronger association between PSC and other autoimmune conditions. We aimed to assess coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune co-morbidity on severe outcomes. Method:In a matched cohort study, 1,378 individuals with PSC and 13,549 general population comparators and their first-degree relatives were evaluated. National registries provided data on diagnoses and outcomes (liver transplantation, hepatobiliary cancer, liver related death). Odds ratio (OR) of autoimmune disease was estimated by logistic regression. Fine & Gray competing risk regression estimated hazard ratios (HRs) for severe outcomes. Results:Prevalence of non-IBD, non-autoimmune hepatitis (AIH), autoimmune disease was 18% in PSC and 11% in comparators, OR 1.77(95%CI; 1.53-2.05). Highest odds were seen for celiac disease [OR 4.36(95%CI; 2.44-7.49)], sarcoidosis [OR 2.74(95%CI; 1.29-5.33)], diabetes type 1 [OR 2.91(95%CI; 2.05-4.05)], and autoimmune skin disease [OR 2.15(95%CI; 1.52-2.96)]. First-degree relatives of individuals with PSC had higher odds for developing IBD, AIH and any autoimmune disease than relatives of the comparators [OR 3.25 95% CI (2.68-3.91); OR 5.94 95% CI (2.82-12.02); OR 1.34 (95% CI: 1.19-1.50)]. Autoimmune co-morbidity in PSC was not associated with poorer outcome, HR 0.96 (95%CI; 0.71-1.28). Conclusion:Individuals with PSC and their first-degree relatives had higher odds for autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcome.