What tests and evaluations are used to diagnose autoimmune hepatitis?

Diagnostic Tests for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a combination of clinical, biochemical, serological, and histological evaluations, with liver biopsy being essential for establishing the diagnosis and determining disease severity. 1

Core Diagnostic Tests

Laboratory Evaluations

• Liver Function Tests:

  • Serum aminotransferases (AST, ALT) - typically elevated, showing predominant aminotransferase abnormality 1
  • Alkaline phosphatase (ALP) - usually less elevated than aminotransferases
  • ALP:AST (or ALT) ratio - typically <1.5 in AIH 1

• Immunoglobulin Assessment:

  • Serum total IgG or γ-globulin levels - elevated >1.5 times upper normal limit in definite AIH 1
  • Any hypergammaglobulinemia supports probable AIH 1

Serological Markers

1. Conventional Autoantibodies (initial testing panel):

   • Antinuclear antibodies (ANA)
   • Smooth muscle antibodies (SMA)
   • Anti-liver/kidney microsome type 1 antibodies (anti-LKM1)
   • Antimitochondrial antibodies (AMA) - to exclude primary biliary cirrhosis 1

2. 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

Histological Assessment

• Liver biopsy - essential for diagnosis and treatment decisions:
  • Interface hepatitis (hallmark feature)
  • Portal plasma cell infiltration (typical but not required)
  • Absence of biliary lesions, granulomas, or other features suggesting alternative diagnoses 1

Exclusion Tests

• Viral Hepatitis Markers:

  • Hepatitis A, B, and C serologies (must be negative) 1

• Metabolic/Genetic Disease Testing:

  • α1-antitrypsin phenotype
  • Serum ceruloplasmin, copper levels (to exclude Wilson disease)
  • Iron studies (to exclude hemochromatosis) 1

• Drug History Assessment:

  • Exclude drug-induced liver injury (minocycline, nitrofurantoin, isoniazid, propylthiouracil, α-methyldopa) 1

Diagnostic Approach

1. Initial Evaluation:

   • Test for conventional autoantibodies (ANA, SMA, anti-LKM1, AMA)
   • Measure serum IgG/γ-globulin levels
   • Assess liver enzymes pattern
   • Exclude viral hepatitis

2. If Initial Tests Inconclusive:

   • Test for supplemental autoantibodies (anti-SLA, pANCA, F-actin, LC1)
   • Apply diagnostic scoring systems

3. Diagnostic Scoring:

   • Original Revised Scoring System (1999): More comprehensive, research-oriented

     • Pretreatment score ≥15 indicates definite AIH (sensitivity 95%, specificity 97%)
     • Pretreatment score 10-15 indicates probable AIH 1

   • Simplified Scoring System (2008): More practical for clinical use

     • ≥7 points: definite AIH (sensitivity 81%, specificity 99%)
     • ≥6 points: probable AIH (sensitivity 88%, specificity 97%) 1, 2

Classification of AIH Types

• Type 1 AIH (80% of cases):

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

• Type 2 AIH:

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

Important Considerations

• Testing Methodology: Autoantibodies should be tested by indirect immunofluorescence at initial dilutions of 1/40 in adults and 1/10 in children using rodent substrate (kidney, liver, and stomach sections) 3

• Diagnostic Pitfalls:

  • Anti-LKM1 can be confused with AMA if only rodent kidney is used 3
  • Simplified criteria may be less accurate in patients with:
    • Acute/fulminant presentation
    • Concomitant cholestatic disease
    • Fatty liver disease
    • Pediatric patients 4

• Special Situations:

  • In patients with AIH and multiple endocrine disorders, test for APECED syndrome by checking for mutations in the AIRE gene 1
  • In seronegative cases with high clinical suspicion, consider a trial of corticosteroid therapy with quick tapering to confirm diagnosis 5

The diagnosis of AIH requires careful integration of all these findings, with liver biopsy remaining a cornerstone of diagnosis to establish the characteristic histological features and exclude alternative diagnoses.