Diagnostic Workup for Autoimmune Hepatitis (AIH)
The diagnosis of autoimmune hepatitis requires a comprehensive laboratory assessment including liver function tests, immunoglobulin levels, autoantibody testing, and liver biopsy, with the latter being essential for definitive diagnosis and treatment decisions. 1, 2
Initial Laboratory Assessment
- Liver function tests should show a predominantly hepatitic pattern with elevated serum aminotransferases (ALT/AST) ranging from just above normal to >50 times normal, with normal or only moderately elevated cholestatic enzymes 1, 2
- Calculate the alkaline phosphatase (ALP) to AST (or ALT) ratio - a ratio <1.5 favors AIH diagnosis 1, 2
- Measure serum immunoglobulin G (IgG) levels, which are typically elevated >1.5 times the upper limit of normal in 85% of AIH cases 1, 3
- Test for viral hepatitis markers (hepatitis A, B, and C) to exclude viral causes 1, 2
- Obtain a detailed medication history to rule out drug-induced hepatitis 1
- Evaluate serum albumin, bilirubin (conjugated and unconjugated) levels 1
- Test for normal serum concentrations of alpha-1-antitrypsin, copper, and ceruloplasmin to exclude other causes of chronic liver disease 1
Autoantibody Testing
First-line autoantibody screening should include: 1, 2
- Antinuclear antibody (ANA)
- Smooth muscle antibody (SMA)
- Anti-liver kidney microsomal type 1 antibody (anti-LKM1)
Second-line autoantibody testing should include: 1, 2, 3
- Anti-liver cytosol type 1 (anti-LC1)
- Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
- Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)
- Use indirect immunofluorescence (IFL) on rodent tissue sections (kidney, liver, and stomach) for ANA, SMA, and anti-LKM1
- Significant titers in adults are ≥1:40 for ANA/SMA and anti-LKM1
- Lower titers (1:20) may be significant in children
- Use ELISA or immunoblotting for anti-SLA/LP detection
Liver Biopsy
- Liver biopsy is mandatory for definitive diagnosis, assessment of disease severity, and treatment decisions 1, 2, 3
- Key histological features to look for include: 1, 2, 5
- Interface hepatitis (hallmark finding)
- Lymphoplasmacytic infiltrates
- Emperipolesis (lymphocytes within hepatocyte cytoplasm)
- Hepatocyte rosettes
- Absence of biliary lesions, granulomas, or other changes suggesting different etiology
Diagnostic Scoring Systems
The Simplified Diagnostic Scoring System includes: 2, 3
- Autoantibody titers
- IgG levels
- Liver histology
- Absence of viral hepatitis
- Score ≥6 indicates probable AIH; score ≥7 indicates definite AIH
The Revised Original Diagnostic Scoring System is more comprehensive and includes: 1
- Gender
- ALP/AST ratio
- IgG levels
- Autoantibody titers
- Viral markers
- Drug history
- Alcohol intake
- Histology
- HLA typing
- Treatment response
- Pre-treatment score >15 indicates definite AIH; 10-15 indicates probable AIH
Additional Testing for Differential Diagnosis
- For cholestatic pattern, test for antimitochondrial antibody (AMA) to evaluate for AIH-PBC overlap 1, 2
- Consider magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiography (ERCP) to evaluate for AIH-PSC overlap 1, 2
- In children with AIH, MRCP is recommended to exclude autoimmune sclerosing cholangitis 1
- In patients with AIH and multiple endocrine disorders, test for APECED syndrome by evaluating mutations in the AIRE gene 1
Common Pitfalls to Avoid
- Overlooking AIH in viral hepatitis-endemic areas 3
- Relying solely on autoantibody testing without considering the entire clinical picture 3, 4
- Missing AIH with normal IgG levels (occurs in 10-25% of cases, particularly in acute presentations) 3, 6
- Failure to obtain liver biopsy, which is essential for definitive diagnosis 1, 2, 3
- Confusing anti-LKM1 with antimitochondrial antibody (AMA) when using rodent kidney as the sole immunofluorescence substrate 4
- Not retesting for autoantibodies in initially seronegative patients, as autoantibody expression can vary during the course of AIH 1, 3