Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Figure 1

Pathogenesis of autoimmune hepatitis. HLA and non-HLA molecules as well as environmental triggers such as viruses, toxins, and the microbiome have been suggested as key components for a T cell-mediated immune response. The presentation of autoantigenic peptide (AG) to naïve CD4⁺ T helper cells (TH0) by antigen-presenting cells (APC, dendritic cells (DC)) leads to a secretion of proinflammatory cytokines (IL-12, IL-6, and TGF-B) who give rise to the development of Th1, Th2, and TH17 cells. TH1 cells secrete IL-2 and IFN-y, which stimulate CD8⁺ cells to induce expression of HLA class I and HLA class II molecules on hepatocytes. Tregs and Th2 cells secrete IL-4, Il-10, and IL-13 thereby stimulating the maturation of B cells and plasma cells which themselves produce autoantibodies. TH17 cells, which increased number correlates with the degree of liver fibrosis, secrete proinflammatory cytokines and suppress T regulatory cells (Treg). The numerical decrease of Tregs leads to impaired tolerance to autoantigens which subsequently results in the initiation and perpetuation of autoimmune liver damage. The histological characteristics of interface hepatitis comprise an inflammatory cell infiltrate consisting of lymphocytes and plasma cells which is located around the portal tracts.