What is the diagnostic approach for autoimmune hepatitis?

Diagnostic Approach for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires liver biopsy showing interface hepatitis, elevated immunoglobulin G (IgG) levels, presence of specific autoantibodies, and exclusion of other causes of liver disease. 1

Key Diagnostic Elements

Clinical Presentation

• Presentation ranges from asymptomatic with abnormal liver tests to acute severe hepatitis
• More common in females
• May have associated extrahepatic autoimmune conditions

Laboratory Assessment

Initial Testing

• Liver biochemistry: Predominantly hepatitic pattern with elevated aminotransferases (AST/ALT)
• Serum IgG or γ-globulin levels: Elevated in 85% of cases (>1.5 times upper limit of normal strongly supports diagnosis) 1
• Conventional autoantibodies panel:
  • Antinuclear antibodies (ANA)
  • Smooth muscle antibodies (SMA)
  • Anti-liver/kidney microsome type 1 (anti-LKM1)
  • Anti-liver cytosol type 1 (anti-LC1)

Autoantibody Testing Interpretation

• In North American adults, 96% of AIH patients have ANA, SMA, or both 1
• Only 4% have anti-LKM1 and/or anti-LC1 1
• Significant titers:
  • Adults: ≥1:40 (probable AIH), ≥1:80 (definite AIH)
  • Children: ≥1:20 1

Additional Autoantibodies (for seronegative cases)

• Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
• Anti-asialoglycoprotein receptor (anti-ASGPR)
• Anti-actin
• Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 1

Histological Assessment

• Liver biopsy is essential for diagnosis and treatment decisions 1
• Key histological features:
  • Interface hepatitis (hallmark finding)
  • Portal plasma cell infiltration (typical but not required)
  • Emperipolesis (active penetration by one cell into another)
  • Hepatic rosette formation 1

Exclusion of Other Liver Diseases

• Viral hepatitis (HAV, HBV, HCV)
• Hereditary disorders:
  • Wilson disease (check ceruloplasmin)
  • Alpha-1 antitrypsin deficiency
  • Genetic hemochromatosis (check iron studies)
• Drug-induced liver injury (minocycline, nitrofurantoin, isoniazid, propylthiouracil, α-methyldopa)
• Alcoholic liver disease
• Non-alcoholic fatty liver disease
• Primary biliary cholangitis (check for AMA)
• Primary sclerosing cholangitis (consider MR cholangiography) 1

Diagnostic Scoring Systems

Simplified Diagnostic Criteria (2008) 1

Parameter	Criteria	Score
Autoantibodies	ANA or SMA ≥1:40	+1*
	ANA or SMA ≥1:80	+2*
	Anti-LKM1 ≥1:40	+2*
	Anti-SLA/LP positive (any titer)	+2*
IgG levels	>Upper limit of normal	+1
	>1.1× upper limit	+2
Liver histology	Compatible with AIH	+1
	Typical of AIH	+2
Absence of viral hepatitis	Yes	+2

*Maximum 2 points for all autoantibodies combined

• Score ≥7: Definite AIH
• Score ≥6: Probable AIH

Common Pitfalls and Caveats

1. Acute presentation: Up to 39% of acute AIH cases may have normal IgG levels 1

2. Seronegative AIH: Patients negative for conventional autoantibodies should be tested for non-standard markers (anti-SLA/LP, pANCA) 1

3. Variant syndromes: Histologic findings like ductopenia or destructive cholangitis may indicate overlap with PSC or PBC 1

4. Diagnostic challenges in children: Consider APECED syndrome (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy) in children with AIH and multiple endocrine disorders by testing for AIRE gene mutations 1

5. Histologic misinterpretation: Steatosis or iron overload may suggest alternative diagnoses like NAFLD, Wilson disease, or hemochromatosis 1

Diagnostic Algorithm

1. Initial evaluation:

   • Liver biochemistry panel
   • IgG/γ-globulin levels
   • Conventional autoantibodies (ANA, SMA, anti-LKM1, anti-LC1)
   • Viral hepatitis markers (HAV, HBV, HCV)
   • Exclude metabolic/genetic liver diseases

2. Liver biopsy: Essential for diagnosis confirmation and assessment of disease severity

3. Apply diagnostic criteria:

   • Use simplified scoring system for routine clinical practice
   • For atypical cases, consider the revised original scoring system

4. For seronegative suspected cases:

   • Test for additional autoantibodies (anti-SLA/LP, pANCA, anti-actin)
   • Consider diagnostic trial of corticosteroids with monitoring of response

5. For suspected variant syndromes:

   • Perform MR cholangiography to exclude sclerosing cholangitis
   • Check for AMA to rule out primary biliary cholangitis