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Autoimmune hepatitis: Pathogenesis

Michael A Heneghan, MD, MMedSc, FRCPI
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology characterized by immunologic and autoimmunologic features, generally including the presence of circulating autoantibodies and a high serum globulin concentration [1]. The current classification of AIH uses the type of circulating autoantibodies that are present, although there is little evidence to support a role for these antibodies in the pathogenesis of this disorder (table 1). Two major forms of AIH have been described: type 1 and type 2. Overlap syndromes also can occur with features of both autoimmune hepatitis and primary biliary cholangitis or primary sclerosing cholangitis. (See "Autoimmune hepatitis: Disease classification".)

Type 1 autoimmune hepatitis – Type 1 or classic AIH is characterized by circulating antibodies to nuclei (ANA), smooth muscle (ASMA), and IgG F actin (AAA). AAA is not generally measured in most clinical laboratories, but ASMA with titers of 1:320 or greater almost always reflect the presence of AAA. One report found that measuring AAA by an ELISA was more sensitive than ASMA by immunofluorescence and similarly specific [2]. (See "Autoimmune hepatitis: Clinical manifestations and diagnosis".)

A number of other autoantibodies also occur in this disorder, including atypical perinuclear antineutrophil cytoplasmic antibodies (atypical pANCA), antibodies to the liver-specific asialoglycoprotein receptor (see 'Relevant autoantigens' below), anti SLA/LP (soluble liver antigens/liver-pancreas antigens), and double-stranded DNA. The presence of AMA (antimitochondrial antibodies) has occasionally been reported but should raise the likelihood of an underlying diagnosis of primary biliary cholangitis.

Type 2 autoimmune hepatitis – Type 2 AIH is defined by the presence of antibodies to liver/kidney microsomes (ALKM-1) and/or to a liver cytosol antigen (ALC-1), and, rarely, to ALKM-3.

The pathogenesis of autoimmune hepatitis will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Autoimmune hepatitis: Clinical manifestations and diagnosis" and "Autoimmune hepatitis: Treatment".)


One theory for the pathogenesis of AIH suggests that the disease is caused by an environmental trigger in a genetically predisposed individual. The exact relationships between the genes and the autoimmune process remain largely undefined, but at the molecular level, they are thought to involve the antigen, the major histocompatibility complex (MHC), and the T cell receptor (TCR). These form a ternary complex in which short segments called complementary determining regions (CDR) identify and contact the antigen-MHC complex. Viruses, drugs, herbs, and immunizations have been suggested as triggering agents but the nature of relevant antigens is still undefined, and in most instances, no specific inducer of autoimmunity can be identified.

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Literature review current through: Nov 2017. | This topic last updated: Apr 05, 2016.
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