Recommended Laboratory Workup for Suspected Autoimmune Hepatitis (AIH)
The recommended laboratory workup for suspected autoimmune hepatitis includes liver function tests, immunoglobulin levels, autoantibody testing, viral hepatitis markers, and liver biopsy, with autoantibody testing being the cornerstone for diagnosis and classification. 1, 2
Initial Laboratory Assessment
- Liver Function Tests: Evaluate for hepatitic pattern with elevated serum AST and ALT levels (can range from slightly elevated to >50 times normal), with normal or only moderately elevated cholestatic enzymes (ALP) 2
- ALP/AST (or ALT) ratio: Calculate this ratio as it contributes to diagnostic scoring (ratio <1.5 favors AIH diagnosis) 1
- Serum Immunoglobulin G (IgG): Measure total IgG levels which are typically elevated in 85% of AIH cases (though may be normal in 10-25% of acute presentations) 2, 3
- Viral Hepatitis Markers: Test for hepatitis A, B, and C to exclude viral causes (negative viral markers support AIH diagnosis) 1, 2
- Exclusion of Drug-Induced Liver Injury: Detailed medication history to rule out drug-induced hepatitis which can mimic AIH 1
Autoantibody Testing
First-line autoantibody screening: 1, 2
- Antinuclear antibody (ANA)
- Smooth muscle antibody (SMA)
Second-line autoantibody testing (if initial screening is negative or to further characterize): 1
- Anti-liver kidney microsome type 1 (anti-LKM1)
- Anti-liver cytosol type 1 (anti-LC1)
- Anti-soluble liver antigen (anti-SLA)
- Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)
- Indirect immunofluorescence on rodent tissue sections (including kidney, liver, and stomach) for ANA, SMA, and anti-LKM1
- ELISA or immunoblotting for anti-SLA detection
- Significant titers in adults: ≥1:40 dilution
- Significant titers in children: 1:20 for ANA/SMA and 1:10 for anti-LKM1
Additional Testing for Overlap Syndromes
- For cholestatic pattern: 1
- Antimitochondrial antibody (AMA) to evaluate for AIH-PBC overlap
- Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiography (ERCP) to evaluate for AIH-PSC overlap
Liver Biopsy
- Mandatory for definitive diagnosis and treatment decisions 1, 2
- Key histological features to evaluate: 1, 2
- Interface hepatitis
- Lymphoplasmacytic infiltrates
- Emperipolesis (active penetration by one cell into and through a larger cell)
- Hepatocyte rosette formation
- Presence/absence of biliary changes
Diagnostic Scoring Systems
Simplified Diagnostic Scoring System: 1, 2
- Includes autoantibodies, IgG levels, liver histology, and absence of viral hepatitis
- Score ≥6: Probable AIH
- Score ≥7: Definite AIH
Revised Original Diagnostic Scoring System: 1
- More comprehensive scoring including gender, ALP/AST ratio, IgG levels, autoantibodies, viral markers, drug history, alcohol intake, histology, HLA typing, and treatment response
- Pre-treatment score >15: Definite AIH
- Pre-treatment score 10-15: Probable AIH
Important Considerations and Pitfalls
- Seronegative AIH: Approximately 10-20% of AIH cases may initially be seronegative, particularly in acute presentations 3, 5
- Autoantibody variability: Titers and specificity may vary during disease course; repeated testing may be necessary if initial results are negative but clinical suspicion remains high 1, 5
- Acute presentation: May have atypical features including normal IgG levels and absence of typical autoantibodies 6, 7
- Reference laboratory testing: Consider sending samples to reference laboratories for comprehensive autoimmune serology workup in cases of diagnostic uncertainty 1, 5
- Post-transplant monitoring: For patients with history of AIH who underwent liver transplantation, regular liver biopsies are warranted as histological recurrence often precedes biochemical abnormalities 8