Concomitant immunological diseases in primary sclerosing cholangitis are a risk factor for reduced survival

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can be rather defined as an immune-mediated disease than a classical autoimmune disease. Association with other immunological diseases like inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) is well known. We evaluated the presence of immunological disease beside IBD and AIH in a German cohort of PSC patients and performed a concise differentiation between classical autoimmune (AID) and immune-mediated inflammatory diseases (IMID) and report its influence on clinical outcome.

Methods: Cohort study of 195 PSC patients that were evaluated over the period 1987–2010 at our tertiary care center. The presence of immunological diseases was determined by chart review. Immunological diseases were sub-classified into AID and IMID, according current guidelines.

Results: 27/195 (13.8%) patients with PSC had at least one additional immunological disease other than IBD (70%) or AIH (3%). The most frequent AIDs were autoimmune thyreopathy (2.6%) and IDDM (2.1%). The most frequent IMIDs were psoriasis (3.6%) and sarcoidosis (2.1%). After more than twenty years of follow up, PSC patients with concomitant immunological diseases had a markedly reduced actuarial transplantation-free survival rate (mean: 8.9 years vs. 16.3 years, p=0.012). Further subgroup analysis revealed a significant reduced survival in patients with concomitant IMID (0.017). By contrast concomitant AID showed no impact on survival.

Conclusion: Concomitant immune-mediated inflammatory diseases but not classical autoimmune diseases represent an independent risk factor for reduced transplantation-free survival in patients with PSC. These findings might point to a new subgroup of patients with a more serious phenotype of PSC.

Literatur: [1] Aron JH, Bowlus CL. The immunobiology of primary sclerosing cholangitis. Semin Immunopathol 2009;31(3): 383-397. [2] Chapman RW, Arborgh BA, Rhodes JM, Summerfield JA, Dick R, Scheuer PJ, et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut 1980;21(10): 870-877. [3] Chapman RW, Varghese Z, Gaul R, Patel G, Kokinon N, Sherlock S. Association of primary sclerosing cholangitis with HLA-B8. Gut 1983;24(1): 38-41. [4] Gotthardt DN, Rudolph G, Kloters-Plachky P, Kulaksiz H, Stiehl A. Endoscopic dilation of dominant stenoses in primary sclerosing cholangitis: outcome after long-term treatment. Gastrointest Endosc 2010;71(3): 527-534. [5] Lamberts LE, Janse M, Haagsma EB, van den Berg AP, Weersma RK. Immune-mediated diseases in primary sclerosing cholangitis. Dig Liver Dis 2011. [6] Melum E, Franke A, Schramm C, Weismuller TJ, Gotthardt DN, Offner FA, et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nat Genet 2011;43(1): 17-19. [7] Rudolph G, Gotthardt D, Kloeters-Plachky P, Rost D, Kulaksiz H, Stiehl A. In PSC with dominant bile duct stenosis, IBD is associated with an increase of carcinomas and reduced survival. J Hepatol 2010;53(2): 313-317. [8] Saarinen S, Olerup O, Broome U. Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis. Am J Gastroenterol 2000;95(11): 3195-3199. [9] Tervaert JW, Mulder AH, Horst G, Haagsma EB, Kleibeuker JH, Kallenberg CG. Antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis, ulcerative colitis, and autoimmune diseases. Gastroenterology 1992;102(3): 1090-1091. [10] Teufel A, Weinmann A, Kahaly GJ, Centner C, Piendl A, Wörns M, Lohse AW, Galle PR, Kanzler S. Concurrent autoimmune diseases in patients with autoimmune hepatitis. J Clin Gastroenterol. 2010 Mar;44(3):208-13. [11] Wiesner RH, Grambsch PM, Dickson ER, Ludwig J, MacCarty RL, Hunter EB, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology 1989;10(4): 430-436.

cholestatic liver disease - immunological disease - primary sclerosing cholangitis