What labs should be checked to diagnose autoimmune hepatitis?

Laboratory Tests for Diagnosing Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a comprehensive panel of tests including liver function tests, immunoglobulins (particularly IgG), conventional autoantibodies (ANA, SMA, anti-LKM1, AMA), and supplemental autoantibodies (anti-SLA/LP, anti-actin, anti-LC1, pANCA) when conventional tests are negative. 1, 2

Initial Laboratory Evaluation

Essential Tests:

• Liver Function Tests

  • Serum AST/ALT (typically elevated)
  • Alkaline phosphatase (AP:AST ratio <1.5 supports AIH) 1
  • Bilirubin

• Immunoglobulins

  • Total IgG (elevated in ~85% of cases, >1.5 times upper limit supports definite AIH) 2
  • γ-globulin levels (elevated in ~85% of patients) 2
  • IgA and IgM (usually normal; elevated IgA suggests alcoholic liver disease; elevated IgM suggests PBC) 2

• Conventional Autoantibodies

  • Antinuclear antibody (ANA)
  • Smooth muscle antibody (SMA)
  • Anti-liver/kidney microsome type 1 (anti-LKM1)
  • Antimitochondrial antibody (AMA) - to exclude PBC 1

Supplemental Autoantibodies (if conventional tests negative):

• Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
• Anti-actin (F-actin)
• Anti-liver cytosol type 1 (anti-LC1)
• Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 1, 2

Exclusion Testing

• Viral Hepatitis Markers

  • Hepatitis A, B, and C serologies (must be negative) 2

• Metabolic/Genetic Disease Testing

  • α1-antitrypsin phenotype
  • Serum ceruloplasmin and copper levels (to exclude Wilson disease)
  • Iron studies (to exclude hemochromatosis) 2

• In patients with multiple endocrine disorders

  • Test for APECED syndrome by checking for mutations in the AIRE gene 1, 2

Interpretation of Results

AIH Classification Based on Autoantibody Profile:

• Type 1 AIH (80% of cases)

  • Positive for ANA and/or SMA
  • More common in adults
  • Often associated with other autoimmune diseases 1, 2

• Type 2 AIH

  • Positive for anti-LKM1 and/or anti-LC1
  • More common in children
  • May have more severe presentation 1, 2

Diagnostic Scoring Systems:

1. Original Revised Scoring System (1999)

   • Definite AIH: ≥15 points
   • Probable AIH: 10-15 points 1, 2

2. Simplified Scoring System (2008)

   • Definite AIH: ≥7 points
   • Probable AIH: ≥6 points 2

Important Considerations

• Liver biopsy is essential for definitive diagnosis, showing interface hepatitis with lymphoplasmacytic infiltrates 1, 2

• In acute or fulminant AIH, approximately 25-39% of patients may have normal IgG levels 2

• Autoantibody testing should be performed by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10 in children 3

• Anti-LKM-1 can be confused with AMA if rodent kidney is used as the sole immunofluorescence substrate 3

Common Pitfalls to Avoid

• Relying solely on conventional autoantibodies; up to 5% of AIH patients may be seronegative for standard markers 2, 4

• Overlooking AIH in patients with normal IgG levels, particularly in acute presentations 2

• Confusing the pattern of immunoglobulin elevation (IgG vs. IgA vs. IgM) when differentiating between AIH and other liver diseases 2

• Failing to test for supplemental autoantibodies when conventional tests are negative but clinical suspicion remains high 1, 2