When to Test for Autoimmune Hepatitis and Characteristic Laboratory Findings
Testing for autoimmune hepatitis (AIH) should be considered in any patient with acute or chronic liver disease, particularly if hypergammaglobulinemia is present, and if the patient has features of other autoimmune diseases. 1
Clinical Scenarios Warranting AIH Testing
- AIH should be considered during the diagnostic workup of any unexplained elevation in liver enzymes, regardless of patient age, sex, or ethnicity 1, 2
- Testing is particularly important in patients with a predominantly hepatitic pattern (elevated AST/ALT with normal or only moderately elevated cholestatic enzymes) 1, 3
- AIH should be suspected in patients with acute hepatitis presentations, as approximately 25% of AIH cases present acutely 1, 4
- Consider testing in patients with other autoimmune diseases, as AIH is associated with a broad variety of autoimmune conditions 1, 5
- All children with suspected AIH should undergo MR-cholangiography to exclude autoimmune sclerosing cholangitis 1
Initial Laboratory Assessment
- Liver function tests showing a hepatitic pattern with elevated serum AST and ALT, ranging from just above normal to >50 times normal 1, 3
- Calculate the ALP/AST (or ALT) ratio, with a ratio <1.5 favoring AIH diagnosis 2, 5
- Serum IgG levels, which are typically elevated in approximately 85% of AIH cases, though may be normal in 10-25% of acute presentations 1, 3, 4
- Viral hepatitis markers (HAV, HBV, HCV) must be negative to support AIH diagnosis 1, 2
- Detailed medication history to rule out drug-induced liver injury that can mimic AIH 2
Autoantibody Testing Protocol
First-line autoantibody screening should include 1, 3:
- Antinuclear antibody (ANA)
- Smooth muscle antibody (SMA)
- Anti-liver kidney microsomal type 1 antibody (anti-LKM1)
Second-line autoantibody testing should include 1, 3:
- Anti-liver cytosol type 1 (anti-LC1)
- Anti-soluble liver antigen/liver pancreas (anti-SLA/LP)
- Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)
Autoantibodies should be tested by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10-1/20 in children on rodent tissue sections that include kidney, liver, and stomach 1, 6
Characteristic Laboratory Findings in AIH
Elevated transaminases (AST, ALT) with AST/ALT ratio typically <1 1, 3
Elevated IgG/gamma-globulin levels (>1.5 times upper limit of normal) in 85% of cases 1, 3
Autoantibody positivity based on AIH type 1:
- Type 1 AIH: Positive for ANA and/or SMA
- Type 2 AIH: Positive for anti-LKM1 and/or anti-LC1
Anti-SLA/LP antibodies may be present in both types and are associated with more severe disease 6
Normal or only moderately elevated alkaline phosphatase and GGT 1
Liver Biopsy
- Liver biopsy is mandatory for definitive diagnosis, showing characteristic findings 2, 3:
- Interface hepatitis
- Lymphoplasmacytic infiltrates
- Emperipolesis (active penetration of one cell by another)
- Plasma cells (present in 86.5% of cases) 4
Diagnostic Scoring Systems
The Simplified Diagnostic Scoring System includes 2, 7:
- Autoantibody titers
- IgG levels
- Liver histology
- Absence of viral hepatitis
- Score ≥6 indicates probable AIH; score ≥7 indicates definite AIH
The Revised Original Scoring System is more comprehensive and includes additional parameters such as gender, ALP/AST ratio, and treatment response 2, 5
Common Pitfalls to Avoid
- Overlooking AIH in patients with acute hepatitis presentation 1, 4
- Missing AIH in patients with normal IgG levels (occurs in up to 25-39% of acute presentations) 3, 4
- Confusing anti-LKM1 with anti-mitochondrial antibody when using only kidney tissue for immunofluorescence 1, 6
- Relying solely on autoantibody testing without considering histology 3
- Failing to test for second-line autoantibodies in patients negative for conventional autoantibodies but with clinical suspicion of AIH 1, 8