Primary Sclerosing Cholangitis in Genetically Diverse Populations Listed for Liver Transplantation: Unique Clinical and Human Leukocyte Antigen Associations

Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic, and African American PSC patients listed for liver transplantation (LT). Population-stratified demographic, clinical, and HLA data from 6767 LT registrants of the United Network for Organ Sharing who had a diagnosis of PSC (4.7% of the registrants) were compared to data from registrants with other diagnoses. Compared to European Americans and Hispanics, African Americans were significantly younger (46.6 ± 13.7, 42.3 ± 15.9, and 39.7 ± 13.1 years, respectively; P = 0.002) and were listed with a higher Model for End-Stage Liver Disease score (15.2 ± 7.5, 14.9 ± 7.6, and 18.1 ± 9.3, respectively; P = 0.001); they were also less frequently noted to have inflammatory bowel disease in comparison with European Americans (71.4% versus 60.5%, P < 0.01). In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (odds ratio with respect to European Americans = 1.325, 95% confidence interval = 1.221-1.438). HLA associations in European Americans, Hispanics, and African Americans with PSC versus alcoholic liver disease were detected for HLA-B8, HLA-DR13, and protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, showed associations only in European Americans and Hispanics. In conclusion, African Americans with PSC who are listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC.