Autoimmune Hepatitis


Autoimmune hepatitis (AIH) is an organ‐specific autoimmune disease resulting from a loss of immunological tolerance against hepatocyte autoantigens. In the absence of treatment, this disease is fatal. Distinctive characteristics of AIH include hypergammaglobulinemia, presence of autoantibodies and interface hepatitis with lymphoplasmacytic infiltrates. AIH is a rare disease with an estimated point prevalence in Europe and North America of 50–200 cases per million. The pathogenesis of AIH remains unknown. AIH is believed to result from a combination of liver‐specific susceptibility factors, faulty immune tolerance mechanisms (central and peripheral) as well as host and environmental susceptibility factors. Patients respond well to immunosuppressive treatment, but 10–20% of patients are unable to achieve remission using standard treatment. Through a better understanding of AIH pathogenesis as well as cellular(s) and molecular(s) effectors involved, new and effective site‐specific immunotherapies are being developed to induce long‐term remission in patients with minimal deleterious side effects.

Key Concepts

  • Autoimmune hepatitis is characterised by a loss of tolerance against hepatocytes leading to the progressive destruction of the hepatic parenchyma.
  • About 70–90% of AIH patients are women.
  • Hallmark characteristics of AIH include hypergammaglobulinemia, presence of autoantibodies and an interface hepatitis with lymphoplasmacytic infiltrates.
  • Type 1 AIH is characterised by the presence of ANA and/or SMA autoantibodies while Type 2 AIH is characterised by the presence of anti‐LKM1 and/or anti‐LC1 autoantibodies.
  • There is a genetic association between AIH and HLA class II genes suggesting a role for CD4+ T cells autoimmune response in AIH pathogenesis.
  • Conventional therapy for AIH patients consists of nonspecific immunosuppression, usually through the use of a combination of prednisone/prednisolone and azathioprine.
  • New biologics‐based specific immunotherapies are currently in development and aim to induce long‐term remission with minimal unwanted side effects.

Keywords: autoimmunity; liver; autoantibody; hepatitis; pathogenesis; immune tolerance

Figure 1. Histology of autoimmune hepatitis. Lymphoplasmacytic infiltration with interface hepatitis and bridging necrosis of hepatic lobules (a). Transformation of hepatocytes into giant cells and significant infiltration of the hepatic lobule (b). Formation of hepatocyte rosettes (c). Reprinted from Clin Liver Dis., 10 (1), Alvarez, F., Autoimmune hepatitis and primary sclerosing cholangitis, 89–107, Copyright (2006), with permission from Elsevier.
Figure 2. Putative mechanisms of liver damage in AIH (autoimmune hepatitis). On the basis of data from experimental model and observations made in patient following specific immunotherapies, we propose the following model for liver damage in AIH. Lacking or defective regulatory CD4+ T cells (green) would allow the activation by antigen‐presenting cells (APC) of autoreactive CD4+ (yellow) and CD8+ (blue) T cells. These autoreactive T cells would then proliferate, secrete proinflammatory cytokines (TNF‐α) and lyse cells by recognising their cognate autoantigen presented by hepatocytes. Autoreactive B cells (pink) would also contribute to the expansion and activation of autoreactive T cells by presenting their recognised autoantigen to autoreactive T cells leading to further hepatocyte lysis.


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Further Reading

Czaja AJ and Manns MP (2010) Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology 139: 58–72.e4.

Liberal R, Grant CR, Mieli‐Vergani G and Vergani D (2013) Autoimmune hepatitis: a comprehensive review. Journal of Autoimmunity 41: 126–139.

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How to Cite close
Lapierre, Pascal(Feb 2018) Autoimmune Hepatitis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026255]