Hepatitis, Autoimmune



A chronic inflammatory disorder of unknown etiology affecting the liver; characterized by periportal necrosis (interface hepatitis or piecemeal necrosis), hypergammaglobulinemia, and autoantibody formation

  • Can be asymptomatic or lead to acute hepatic failure
  • Diagnosis of autoimmune hepatitis (AIH) is based on clinical, histologic, biochemical, and immunologic criteria.


0.1 to 2/100,000 per year in Caucasians. Highest incidence in Northern Europeans; lower in Japanese


  • 11 to 17/100,000 in Europe
  • Female > male (type I: 4:1; type II: 10:1)
  • Bimodal age distribution for type I: Adolescents and adults in the 4th to 6th decades are most at risk.
  • Type II is more common in Southern Europe; primarily affects young females and children

Etiology and Pathophysiology

  • Hepatic damage is cell mediated.
    • Human leukocyte antigen (HLA) engages antigen-processing cells to stimulate cytotoxic T-cell response.
    • Cytotoxic T lymphocytes infiltrate hepatic tissue, releasing cytokines and damaging hepatocytes.
    • Chronic hepatic inflammation leads to fibrosis and cirrhosis in advanced cases.
  • Fulminant inflammation can lead to acute liver failure without cirrhosis.
  • Type I (80% of cases): circulating anti–smooth muscle antibodies (ASMAs) and/or antinuclear antibodies (ANAs)
  • Type II: antibodies to liver/kidney microsome type I (anti-LKM-1)
  • Type III (least understood): soluble liver antigen/liver pancreas antigen (SLA/LP); clinically similar to type I but with different antibody profile
  • Idiopathic

Associated with HLA haplotypes DR3, DR4 in white Northern Europeans (1)

Risk Factors

  • Female
  • Triggers include medications and viruses (herpes simplex, acute hepatitis A or B, Epstein-Barr, cytomegalovirus).
  • Associated autoimmune conditions

Commonly Associated Conditions

  • Type 1 diabetes mellitus
  • Autoimmune thyroiditis
  • Immune-mediated hemolytic anemia
  • Idiopathic thrombocytopenic purpura
  • Celiac sprue; ulcerative colitis
  • Rheumatoid arthritis, vitiligo
  • Primary biliary cirrhosis and primary sclerosing cholangitis occasionally overlap with AIH (1).

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