What lab test checks for autoimmune hepatitis?

Laboratory Testing for Autoimmune Hepatitis

The initial serological battery for diagnosing autoimmune hepatitis should include antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and anti-liver kidney microsome type 1 (anti-LKM1), combined with serum IgG levels and liver transaminases (AST/ALT). 1, 2

Primary Screening Tests

First-Line Autoantibody Panel

In adults, test ANA and SMA first; if these are negative, then assess anti-LKM1. 1, 2 In pediatric patients, all three antibodies (ANA, SMA, and anti-LKM1) should be tested simultaneously at presentation. 1, 2

• ANA is detected in 80% of white North American adults with type 1 AIH at presentation. 2
• SMA is present in 63% of patients with type 1 AIH. 2
• Together, ANA and/or SMA are present in 96% of North American adults with type 1 AIH. 2
• Diagnostic accuracy improves from 58% to 74% when two autoantibodies are detected concurrently. 1, 2

Biochemical Markers

• Elevated serum AST and ALT levels are characteristic findings. 1
• Elevated serum IgG or γ-globulin is typical, though IgG can be normal in approximately 10% of European patients and 25-39% of acute presentations. 2
• An alkaline phosphatase to AST ratio <1.5 supports AIH diagnosis, while a ratio >3 argues against it. 2

Testing Method Requirements

Autoantibodies must be tested by indirect immunofluorescence (IIF) at an initial dilution of 1:40 in adults and 1:10 in children. 1, 3 The substrate should be freshly prepared rodent tissue including kidney, liver, and stomach sections to allow simultaneous detection of all relevant reactivities. 1, 3

• ELISA-based ANA testing should not be used as the sole screening method because it can result in false negatives in approximately one-third of patients. 4
• Indirect immunofluorescence using HEp-2 cells remains the reference standard for ANA detection. 4

Disease Subtype Classification

Type 1 AIH

• Characterized by ANA and/or SMA/anti-actin antibodies. 1, 3
• Represents the majority of AIH cases in North America. 2

Type 2 AIH

• Characterized by anti-LKM1 and/or anti-liver cytosol type 1 (anti-LC1) antibodies. 1, 2, 3
• Anti-LKM1 is present in only 3% of North American adults but is more frequent in European patients. 2
• Anti-LC1 is present in 30% of type 2 AIH cases. 2
• These antibodies are commonly detected in the absence of ANA and SMA. 1, 2

Additional Testing for Seronegative Cases

When conventional antibodies (ANA, SMA, anti-LKM1) are negative but clinical suspicion remains high, additional testing should include:

• Anti-soluble liver antigen (anti-SLA): Has 99% specificity for AIH and is present in 7-22% of type 1 AIH patients; can be the sole marker in 14-20% of AIH cases. 1, 2
• Atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA): Present in 50-92% of type 1 AIH patients and can be the only serological marker in 20-96% of suspected AIH cases with negative conventional antibodies. 1, 2, 4
• Anti-actin antibodies: A subset of SMA present in 86-100% of patients with AIH who have SMA. 1

Critical Diagnostic Pitfalls

Approximately 19-34% of AIH cases can have negative ANA results despite being clinically and pathologically compatible with the disease. 4 In acute severe presentations, 29-39% of patients can show negative or weakly positive ANA results. 4

• Do not exclude AIH based solely on negative ANA, as approximately 20% of AIH patients may be negative for ANA, SMA, and anti-LKM1. 4
• Anti-LKM1 can be confused with anti-mitochondrial antibodies (AMA) if rodent kidney is the sole substrate; kidney sections must include both medulla and cortex to distinguish these patterns. 1, 2, 3
• Anti-LKM1 can occur in 5-10% of chronic hepatitis C patients, making viral hepatitis exclusion crucial. 2

Essential Complementary Testing

Liver biopsy is considered a prerequisite for AIH diagnosis and should be performed before starting treatment. 1, 2 Interface hepatitis with lymphoplasmocytic infiltrates is the hallmark histological finding, though no feature is pathognomonic. 1

Exclusions Required Before Diagnosis

The following must be excluded before diagnosing AIH: viral hepatitis (hepatitis B, C, E), drug-induced liver injury, Wilson's disease, hereditary hemochromatosis, alpha-1 antitrypsin deficiency, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cholangitis, and primary sclerosing cholangitis. 2

Specialized Laboratory Referral

When diagnosis is uncertain or conventional testing is negative despite high clinical suspicion, patient sera should be sent to reference laboratories with expertise in complete autoimmune serology characterization. 1, 4