Hepatitis, Autoimmune - AIH

Hepatitis, Autoimmune - AIH

 

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease of unknown etiology.

Epidemiology

  • Incidence – 2/100,000
  • Sex – F:M; 3:1
  • Type 1 – most common form of AIH
    • Also referred to as classic, active chronic, lupoid, plasma cell, or autoimmune chronic active hepatitis
    • Typically seen in young women
    • Age – bimodal peaks (10-20 years, 45-70 years)
  • Type 2
    • Often seen in children and persons from Mediterranean countries
    • May be seen in association with chronic hepatitis C infection
    • Disease has a rapid onset and progression
  • Type 3
    • Least common form of AIH
    • Typically seen in young women
    • Similar disease course to AIH, type 1

Clinical Presentation

  • Nonspecific – fatigue, lethargy, anorexia, malaise
  • Gastrointestinal – nausea, abdominal pain, jaundice, hepatomegaly
  • Musculoskeletal – arthralgias

Diagnosis

  • No single diagnostic test for AIH
    • Requires evaluation of clinical, laboratory, and histological findings as well as the exclusion of other causes of chronic hepatitis
    • Presenting symptoms can be quite varied –  about 10-30% of patients with clinical features of AIH do not show significant titers of antibodies to any of the markers
  • Laboratory Testing
    • Abnormal liver function tests
    • Elevated gammaglobulins
    • May have positive ANA homogenous pattern, rheumatoid factor
    • Antibodies
      • LKM-1 antibodies
        • React uniformly with cytochrome P450 2D6, a 50kDA protein found in the cytoplasm of all hepatocytes and renal proximal tubular cells
        • In the U.S., LKM-1 antibodies are common in pediatric patients and rare in adults
        • LKM-1 antibodies occur in only 4% of adults with AIH
      • Smooth muscle antibodies (F-actin)
        • SMA antibodies are the hallmark of AIH type 1
        • Also seen in chronic hepatitis
        • Testing LKM positive patients for ANA and SMA may be helpful in distinguishing between type 1 and type 2 AIH
      • Soluble liver antigen (SLA)
        • The presence of SLA antibodies has almost 100% specificity for autoimmune hepatitis, although only 12-30% of patients have these antibodies
Antibody Patterns
AIH Type ANA SMA pANCA* LKM1 SLA LC-1
1 + + +/- - +/- -
2 - - +/- + - +
3 - - +/- - + -
*May be an atypical pANCA staining pattern which disappears after formalin treatment

Differential Diagnosis

  • Important to differentiate AIH from primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), chronic hepatitis, Wilson disease and hemochromatosis

Treatment

  • Therapeutic response to anti-inflammatory therapy may be the only indication of AIH in those patients
  • Treatment differs dramatically for AIH compared to viral hepatitis
    • Immunosuppression used for AIH can be harmful in cases of viral infection and treatment with interferon may cause a worsening of AIH
    • Immunosuppressive treatment is essential in AIH to prevent liver fibrosis and cirrhosis

See Also