What are the diagnostic tests for autoimmune hepatitis?

Diagnostic Tests for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a comprehensive laboratory workup including liver biochemistry tests, immunoglobulin levels, autoantibody testing, viral hepatitis markers, and a liver biopsy, which is considered essential for definitive diagnosis. 1

Essential Laboratory Tests

Autoantibody Testing

• Initial autoantibody panel:

  • Test by indirect immunofluorescence at initial dilution of 1/40 in adults and 1/10 in children 1, 2
  • Use freshly prepared rodent substrate including kidney, liver, and stomach sections 1
  • Test for:
    • Antinuclear antibodies (ANA)
    • Smooth muscle antibodies (SMA)
    • Anti-liver/kidney microsome type 1 antibodies (anti-LKM1)
    • Antimitochondrial antibodies (AMA) to exclude primary biliary cholangitis 3, 1

• Supplemental autoantibodies (if conventional tests are negative):

  • Anti-soluble liver antigen/liver pancreas (anti-SLA/LP) - high specificity (99%) 3, 1
  • Anti-actin (F-actin) - present in 86-100% of patients with AIH and SMA 3
  • Anti-liver cytosol type 1 (anti-LC1) 3, 1
  • Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 3, 1

Other Laboratory Tests

• Serum IgG or γ-globulin levels (elevated in ~85% of patients) 1
• Liver enzymes (AST, ALT, alkaline phosphatase, bilirubin)
• Complete blood count
• Viral hepatitis markers (HAV, HBV, HCV) to exclude viral hepatitis 1
• Metabolic and genetic disease testing:
  • α1-antitrypsin phenotype
  • Serum ceruloplasmin and copper levels (to exclude Wilson's disease)
  • Iron studies (to exclude hemochromatosis) 1

Liver Biopsy

• Essential for definitive diagnosis 3, 1, 4
• Key histological features:
  • Interface hepatitis
  • Dense plasma cell-rich lymphoplasmocytic infiltrates
  • Hepatocellular rosette formation
  • Emperipolesis (penetration of one cell by another)
  • Absence of biliary lesions, granulomas, or other features suggesting alternative diagnoses 1

Diagnostic Scoring Systems

Original Revised Scoring System (1999)

• More comprehensive and research-oriented
• Pretreatment score ≥15 indicates definite AIH (sensitivity 95%, specificity 97%)
• Score of 10-15 indicates probable AIH 3, 1

Simplified Scoring System (2008)

• More practical for clinical use
• ≥7 points indicates definite AIH (sensitivity 81%, specificity 99%)
• ≥6 points indicates probable AIH 1
• Components include:
  • Autoantibody titers
  • IgG levels
  • Liver histology
  • Absence of viral hepatitis 3, 1

AIH Types Based on Autoantibody Profiles

Type 1 AIH (80% of cases)

• Characterized by ANA and/or SMA positivity
• More common in adults
• Often associated with other autoimmune diseases 1

Type 2 AIH

• Characterized by anti-LKM1 and/or anti-LC1 positivity
• More common in children
• May have more severe presentation 1

Special Considerations

• All children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1
• In cases of diagnostic uncertainty, samples should be sent to reference laboratories 1
• Anti-LKM-1 is often confused with AMA if rodent kidney is used as the sole immunofluorescence substrate 2
• Consider testing for APECED syndrome (checking for mutations in the AIRE gene) in patients with AIH and multiple endocrine disorders 1

Common Pitfalls to Avoid

1. Failing to consider AIH in patients with acute presentation (may not meet typical scoring criteria) 5
2. Confusing anti-LKM1 with AMA on immunofluorescence testing 2
3. Relying solely on autoantibody testing without histological confirmation 4
4. Not excluding viral hepatitis, drug-induced liver injury, and metabolic liver diseases 3
5. Missing overlap syndromes with primary biliary cholangitis or primary sclerosing cholangitis 6

Following this diagnostic approach will help ensure accurate diagnosis of AIH, which is crucial as the disease responds well to immunosuppressive treatment when initiated promptly 2.