Programs in Autoimmune Liver Diseases

Three distinct chronic inflammatory conditions affecting the liver: primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and a condition with mixed features, the overlap syndrome, have been described. The etiology and pathogenesis of each is poorly understood. Genetic susceptibility factors, immune dysfunction, infectious agents, and environmental toxins have all been implicated in the etiology and pathogenesis of these diseases.  

Treatment for each disease is suboptimal and a significant fraction of patients still progress to cirrhosis and require liver transplantation. To improve the care of individuals with these diseases, a concerted effort has been undertaken to bring physicians and researchers together with varied expertise to tackle the many questions that remain unanswered in regard to these diseases.

Mount Sinai has had a major and productive interest in primary biliary cholangitis (PBC) for nearly 50 years, with important studies by Drs. Popper and Schaffner illuminating its clinical spectrum, natural history, and histopathologic evolution, as well as the nature and significance of cholestasis. Mount Sinai is currently following as many as 600 patients with this uncommon disease, including more than 100 who have received liver transplants and a similar number with advanced disease currently followed in the pre-transplant clinic.  PBC support group meetings are held monthly at Mount Sinai under the direction of a non-physician moderator. Dr. Nancy Bach acts as a physician advisor.

Primary Sclerosing Cholangitis (PSC) presents unique management issues requiring a multi-disciplinary approach due to its association with inflammatory bowel disease, cholangiocarcinoma, advanced endoscopy, adult and pediatric medicine, and liver transplantation, including liver donor transplantation.  Mount Sinai is one of the few medical centers with expertise in all of these areas. Consequently hundreds of individuals with this rare disease are cared for at Mount Sinai. Those diagnosed as youths are seamlessly transitioned to adult care when necessary.

Autoimmune hepatitis (AIH) presents in many different ways, from benign increases in blood test results to acute liver failure.  Mount Sinai, as a transplant center, is prepared to care for patients at any stage of this disease. Similarly, autoimmune hepatitis is the end result of a number of different inciting factors, one of which is drug induced autoimmune hepatitis, in which Mount Sinai has a particular interest.

Ongoing projects from animal model development to clinical trials of novel therapies are all aimed at reducing the toll these often devastating diseases take on the lives of our patients. The program supports both clinical and basic science initiatives with funds provided by the National Institutes of Health, private foundations and pharmaceutical companies.

  1. Bach N, Schaffner F. Familial primary biliary cirrhosis. J Hepatology 1994; 20: 698-701.

  2. Bach N, Schaffner F. The histological effects of low dose methotrexate therapy for primary biliary cirrhosis. Arch Pathol Lab Med 1998; 122: 342-345.

  3. Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A. Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. J Clin Invest 2001; 108: 223-232.

  4. Schiano TD, Te HS, Thomas RM, Hussain H, Bond K, Black M. Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. Am J Gastroenterol. 2001 Oct;96(10):2984-91.

  5. Ahmad J, Slivka A. Hepatobiliary disease in inflammatory bowel disease. Gastroenterol Clin North Am. 2002 Mar;31(1):329-45. Review.

  6. Bach N, Bodian C, Bodenheimer H, Croen E, Berk PD, Thung SN, Lindor K, Therneau T, Schaffner F. Methotrexate therapy for primary biliary cirrhosis. American J Gastroenterol 2003; 98: 1-7.

  7. Ala A, Stanca CM, Bu-Ghanim M, Ahmado I, Branch AD, Schiano TD, Odin JA, Bach N. Increased prevalence of primary biliary cirrhosis near superfund toxic waste sites. Hepatology 2006; 43: 525-531.

  8. Fiel MI, Agarwal K, Stanca C, Elhajj N, Kontorinis N, Thung SN, Schiano TD. Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus. Liver Transpl. 2008 Jun;14(6):861-71.

  9. Stanca CM, Babar J, Singal V, Ozdenerol E, Odin JA. Pathogenic role of environmental toxins in immune-mediated liver diseases. J Immunotoxicol. 2008 Jan;5(1):59-68.

  10. Hytiroglou P, Gutierrez JA, Freni M, Odin JA, Stanca CM, Merati S, Schiano TD, Branch AD, Thung SN. Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after livertransplant: A blind histologic study. Hepatol Res. 2009 Jun;39(6):577-84.

  11. Fiel MI, Schiano TD. Plasma cell hepatitis (de-novo autoimmune hepatitis) developing post liver transplantation. Curr Opin Organ Transplant. 2012 Jun;17(3):287-92.

  12. Hirschfield GM, Xie G, Lu E, Sun Y, Juran BD, Chellappa V, Coltescu C, Mason AL, Milkiewicz P, Myers RP, Odin JA, Luketic VA, Bacon B, Bodenheimer H, Liakina V, Vincent C, Levy C, Pillai S, Lazaridis KN, Amos CI, Siminovitch KA. Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes Immun. 2012 Jun;13(4):328-35. doi: 10.1038/gene.2011.89. Epub 2012 Jan 19.

  13. Simoes P, Kesar V, Ahmad J. Spectrum of biliary complications following live donor liver transplantation. World J Hepatol. 2015 Jul 18;7(14):1856-65.

  14. Cordell HJ, Han Y, Mells GF, Li Y, Hirschfield GM, Greene CS, Xie G, Juran BD, Zhu D, Qian DC, Floyd JA, Morley KI, Prati D, Lleo A, Cusi D; Canadian-US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium, Gershwin ME, Anderson CA, Lazaridis KN, Invernizzi P, Seldin MF, Sandford RN, Amos CI, Siminovitch KA. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nat Commun. 2015 Sep 22;6:8019.

Joseph A. Odin, MD, PhD
Research Director
Associate Professor of Medicine

Nancy Bach, MD
Clinical Director
Assistant Clinical Professor of Medicine

M. Isabel Fiel, MD
Pathology Director
Professor of Pathology

Jawad Ahmad, MD
Endoscopy Director
Professor of Medicine

Thomas Schiano, MD
Medical Director of Adult Liver Transplantation
Professor of Medicine

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