Advances in the Diagnosis, Pathogenesis, and Management of Autoimmune Hepatitis  Albert J. Czaja, Michael P. Manns  Gastroenterology  Volume 139, Issue 1, Pages 58-72.e4 (July 2010) DOI: 10.1053/j.gastro.2010.04.053 Copyright © 2010 AGA Institute Terms and Conditions

Figure 1 Flow chart of therapy for AIH. Patients are given only corticosteroids or a lower dose of corticosteroids in combination with azathioprine (preferred initial regimen). The outcomes of initial therapy dictate changes in the treatment strategy. Gastroenterology 2010 139, 58-72.e4DOI: (10.1053/j.gastro.2010.04.053) Copyright © 2010 AGA Institute Terms and Conditions

Figure 2 Putative pathogenic pathways of AIH. The antigenic peptide (a self-antigen or foreign antigen that resembles a self-antigen) is displayed in the antigen-binding groove of a class II molecule of the MHC. Genetic factors, especially DRB1*0301 and DRB1*0401 in white North American and northern European adults, encode the structure of the antigen-binding groove and affect the nature of the antigen that can be accommodated. Recognition of the antigen display on the surface of the antigen-presenting cell (APC) by the CD4+ T-cell completes the first costimulatory signal necessary for immunocyte activation (1st signal). Ligation of a B7 molecule on the surface of the APC with the CD28 molecule on the surface of the CD4+ T cell completes the second costimulatory signal necessary for immunocyte activation (2nd signal). The activated CD4+ T cells produce signature cytokines that facilitate the clonal expansion of liver-infiltrating cytotoxic T cells (type 1 cytokine response) or plasma cells that produce Ig (type 2 cytokine response). Deficiencies in the number and function of the Treg cells and NK cells and genetic polymorphisms in TNFA*2 and TNFRSF6 increase the type 1 cytokine response and proliferation of liver-infiltrating cytotoxic T cells. Hepatocyte apoptosis is accomplished by binding of the Fas ligand of the cytotoxic T cell to the Fas molecule on the hepatocyte surface (cell-mediated cytotoxicity). The Igs produced by the expanded clone of plasma cells, possibly as a consequence of deficient Treg and NKT cell function, bind to normal constituents of the hepatocyte membrane and attract NK cells with Fc receptors. The hepatocytes undergo cytolysis (antibody-mediated cellular cytotoxicity). IgG4 staining can be used to characterize some of the plasma cells. Gastroenterology 2010 139, 58-72.e4DOI: (10.1053/j.gastro.2010.04.053) Copyright © 2010 AGA Institute Terms and Conditions