Description

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.

Epidemiology

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

Prevalence

• 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

Genetics
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).