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This chapter discusses a group of conditions that result in chronic inflammation of the liver, ultimately leading to fibrosis, cirrhosis, and liver failure. The epidemiology, pathogenesis, and management of autoimmune hepatitis, Wilson disease, and α1-antitrypsin deficiency are described.

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Essentials of Diagnosis

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  • Characterized by the presence of autoantibodies and elevated serum IgG levels.
  • More common in women than in men.
  • Diagnosis is made on the basis of serologic findings (abnormal liver biochemical tests, autoantibodies, elevated IgG) and histologic findings, and by ruling out other chronic liver diseases (drug-induced liver injury, viral hepatitis, inherited and metabolic liver disorders).
  • Overlap syndromes include features of other chronic liver disorders (eg, primary biliary cirrhosis, primary sclerosing cholangitis).

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General Considerations

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Autoimmune hepatitis (AIH) is a heterogeneous group of chronic inflammatory hepatic disorders identified by the presence of circulating autoantibodies and elevated serum γ-globulins. The pathogenesis of the disease is unclear, although it is believed that genetic predisposition in susceptible individuals ultimately leads to an immunologic process directed against hepatocytes. Among the many suspected inciting factors in those genetically predisposed are toxins and infectious agents. The inflammatory disorder can result in hepatocellular necrosis and collapse or in fibrosis and cirrhosis. The disease is present in all racial groups and all age groups but is more common in women than in men, with a frequency of 3.6:1. It is responsible for approximately 5.9% of the liver transplantations performed in the United States.

Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354:54–66.   [PubMed: 16394302]
Manns, MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193–2213.   [PubMed: 20513004]

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Pathogenesis

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The mechanism of hepatic injury in AIH is not well characterized. There appear to be both genetic and environmental influences.

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AIH is classified into two distinct sub-types based on the presence of autoantibodies. The clinical relevance of this classification system is, however, unclear as it is not certain that autoantibodies play a role in disease pathogenesis. Type 1 disease is present in patients who test positive for antinuclear antibody (ANA) or anti–smooth muscle antibody (ASMA), or both. This is the most common form and has been linked to HLA DRB 10301 (DR3) and DRB 10401 (DR4). Type 2 disease is present in patients who are positive for anti–liver kidney microsomal (ALKM) antibody. This form is common in Europe and is often present in younger women in the second and third decades of life. The linkage is to HLA DRB 10701. A third variant (Type 3) characterized by the presence of antibody to the soluble liver antigen (ASLA) has been abandoned because the ASLA is also present in some patients with Type 1 or Type 2 AIH. Currently, ASLA is touted as a possible prognostic marker for identifying patients who may relapse after cessation of corticosteroid therapy.

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