Earliest descriptions include those by Amberg in 1942 [1] and Leber in 1950 [2] describing a form of chronic liver disease prevalent among young women and characterized by an excessive increase in serum protein and gamma-globulins. risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief conversation of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients. 1. Background Autoimmune hepatitis (AIH) is usually a chronic inflammatory disease of unknown etiology characterized by the presence of circulating autoantibodies, hypergammaglobulinemia, necroinflammatory changes on hepatic histology, and a dramatic response to immunosuppressive therapy. Earliest descriptions include Chlormadinone acetate those by Amberg in 1942 [1] and Leber in 1950 [2] describing a form of chronic liver disease prevalent among young women and characterized by an excessive increase in serum protein and gamma-globulins. In 1951, Kunkel et al. termed the condition hypergammaglobulinemic chronic hepatitis [3]. Since then, it has been known by numerous names including chronic active hepatitis, chronic aggressive hepatitis, plasma cell hepatitis, and autoimmune chronic active hepatitis. Cowling and Mackay coined the term lupoid hepatitis after they noted the association of this entity with autoimmune syndromes and the LE cell phenomenon [4]. The disease is rare with a mean incidence of 1-2 per 100,000 and a point prevalence of 11C17 per 100,000 [5, 6]. Although more frequently seen in young women (sex ratio 3.6?:?1), it can impact children and adults of all ages and ethnicities [7, 8]. A minority of patients may present with acute liver failure and need liver transplantation, but for the majority, the prognosis of AIH is usually good and mostly determined by response to corticosteroid therapy. In general, long-term survival and average life expectancy are excellent and estimated to be comparable to the normal populace [9]. 2. Classification The classification of AIH into different types is based on serum autoantibody profiles. Type I AIH is usually characterized by the presence of antinuclear antibody (ANA), anti-smooth muscle mass antibody (SMA), or both and constitutes 80% of AIH cases. About 25% have cirrhosis at presentation, and association with other autoimmune diseases is usually common (celiac disease, ulcerative colitis, autoimmune thyroid disease) [10, 11]. Type 2 AIH is usually characterized by the presence of anti-liver Chlormadinone acetate kidney microsomal (LKM) 1 and/or anti-LKM3 and/or anti-liver cytosol 1 (LC1) [12, 13] antibodies. Most patients are children, acute severe presentation can occur, and progression to cirrhosis generally ensues [14]. In patients who are unfavorable for standard antibodies and AIH is usually strongly suspected, additional tests can be done including perinuclear antineutrophil cytoplasmic antibodies (pANCA), actin (anti-actin), soluble liver antigen (anti-SLA), asialoglycoprotein receptor (anti-ASGPR), chromatin, and liver cytosol type 1 (anti-LC1). In our experience, 10C15% patients do not have either ANA, SMA, or anti-LKM1 at presentation, but 25% of these will have detectable standard antibodies later in their course. Another 10C20% of the seronegative patients at presentation will have pANCA or anti-SLA. Overall, approximately 5% will have no currently available markers long term. 2.1. Etiopathogenesis Although the exact etiopathogenesis is unknown, AIH, like many autoimmune diseases, is usually thought to be caused by environmental triggers and failure of immune tolerance mechanisms in a genetically susceptible host. These triggers may be of viral or drug etiology, Icam2 but Chlormadinone acetate most Chlormadinone acetate cases have an unknown trigger. Triggers may share epitopes that resemble self-antigens, and molecular mimicry between foreign antigens and self-antigens is the most frequently proposed initiating mechanism in type 2 AIH where the autoantigen is known. Repeated exposures to the triggering antigen, in turn, may trigger autoreactive organ-specific responses. 2.2. Genetic Associations AIH is usually a complex polygenic disease and different populations may have different genetic and environmental triggers and genetic association varies in study populations. The human leukocyte antigen (HLA) genes on chromosome 6 are the most commonly explained association with AIH. HLA associations vary by ethnicity and have been summarized in Table 1. HLA may be associated with age at presentation, disease severity, and response to therapy. How the HLA genes predispose to disease is not exactly known but is likely due to their role in autoreactive T cell selection and autoantigenic peptide presentation. Different susceptibility alleles like HLA DR[44]. In addition CD8+ T cells have been isolated from portal tract infiltrate. CD8 T cells have cytotoxic capability, are capable of secreting IFN-globulin and IgG at presentation[38] Globulins Combination therapy30?mg 1 week50?mg60?mg 1 week 20?mg 1 week50?mg40?mg 1 week15?mg 2 weeks50?mg 30?mg 2 weeks10?mg maintenance dose50?mg20?mg maintenance dose Open in a separate window Prednisone is used alone in patients with severe cytopenias, active malignancy, pregnant or contemplating pregnancy, and those with total thiomethylpurine transferase (TPMT) enzyme deficiency. Combination therapy.