Description

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder of the liver of unknown etiology, characterized by interface hepatitis, hypergammaglobulinemia, and autoantibodies:

• Clinical presentation can range from asymptomatic to acute, severe disease.
• AIH is diagnosed based on clinical, histologic, biochemical, and immunologic criteria.

Epidemiology

Incidence
0.1–1.9/100,000/year in Caucasian populations. Lower incidence in Japan.

• 11.6–16.9/100,000 in Europe
• Females more affected than men for all types of AIH (3.6:1)
• Most common in Caucasians of northern European descent
• Bimodal age distribution for type I: Adolescents and adults in the 4th–6th decades are most at risk.
• Type II is more often found in southern Europe vs. northern Europe, the US, or Japan. Primarily affects young females and children.

Risk Factors

• Female sex
• Triggers include medications, viruses (acute hepatitis A or B, Epstein-Barr)
• Associated autoimmune conditions

• Associated with the complement allele C4AQO and with human leukocyte antigen (HLA) haplotypes B8, B14, DR3, DR4, and Dw3
• Studies show associations between microsatellite markers on chromosomes 11 and 18 (D11S902 and D18S464) and type I AIH (1).

Pathophysiology

• Hepatic damage results from cell-mediated immunologic attack:
  • HLA facilitates presentation to antigen-processing cells, which encourage cytotoxic T-cell production.
  • Cytotoxic T-lymphocytes infiltrate hepatic tissue, release cytokines, and destroy hepatocytes.
  • Chronic inflammation of the liver leads to fibrosis and eventually cirrhosis in advanced cases.
• Acute fulminant inflammation can lead to acute liver failure in the absence of cirrhosis.
• Type I (80% of cases): Circulating antismooth muscle antibodies (SMA) and/or antinuclear antibodies (ANA)
• Type II: Antibodies to liver/kidney microsome type 1 (anti-LKM-1):
• Type III (least well-established type): Soluble liver antigen/liver pancreas antigen (SLA/LP); clinically identical to type I, but with different antibody profile

Etiology

Idiopathic

Commonly Associated Conditions

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