What is the workup for autoimmune hepatitis?

Autoimmune Hepatitis Workup

The diagnostic workup for autoimmune hepatitis (AIH) requires a combination of autoantibody testing, immunoglobulin levels, liver function tests, and liver biopsy, with the latter being essential for definitive diagnosis and treatment decisions. 1

Initial Laboratory Evaluation

• Liver Function Tests: A predominantly hepatitic pattern with elevated aminotransferases (ALT/AST) ranging from just above normal to >50 times normal, with normal or only moderately elevated cholestatic enzymes 1

• Immunoglobulin Assessment: Measure serum IgG levels - hypergammaglobulinemia (elevated IgG) is present in approximately 85% of patients, though may be normal in 10-25% of cases, particularly in acute presentations 1

• Autoantibody Testing: Initial screening should include 1:

  • Antinuclear antibody (ANA)
  • Smooth muscle antibody (SMA)
  • Anti-liver kidney microsomal type 1 antibody (anti-LKM1)
  • Anti-soluble liver antigen (anti-SLA/LP)

• Viral Hepatitis Markers: Must exclude hepatitis A, B, and C infection 1

• Additional Laboratory Tests: To exclude other liver diseases 1:

  • Alpha-1 antitrypsin levels
  • Ceruloplasmin and copper studies
  • Iron studies (ferritin, transferrin saturation)
  • Assessment of alcohol consumption

Autoantibody Testing Protocol

• Indirect Immunofluorescence (IFL) is the preferred initial screening method for ANA, SMA, and anti-LKM1 using rodent tissue sections 1

• Significant titers in adults are ≥1:40 dilution by IFL; in children, titers of 1:20 for ANA/SMA and 1:10 for anti-LKM1 are significant 1

• If initial testing is negative but AIH is still suspected, repeat testing should be performed in a specialty lab including 1:

  • pANCA
  • Specific immunoassays for LKM1, LKM3, LC1, SLA/LP
  • F-actin, Ro52, gp210, sp100

• ELISA or immunoblotting should be used for anti-SLA/LP detection, as IFL cannot detect these antibodies 1

Liver Biopsy

• Liver biopsy is mandatory for definitive diagnosis, assessment of disease severity, and treatment decisions 1

• Characteristic histological findings include 1, 2:

  • Interface hepatitis (hepatitis at the portal-parenchymal interface)
  • Dense plasma cell-rich lymphoplasmocytic infiltrates
  • Hepatocellular rosette formation
  • Emperipolesis (active penetration by one cell into and through a larger cell)
  • Hepatocyte swelling and/or pycnotic necrosis

• Alternative biopsy approaches when coagulopathy is present 1:

  • Transjugular approach
  • Mini-laparoscopy under visual control

Diagnostic Criteria

• Simplified Diagnostic Criteria (International Autoimmune Hepatitis Group) includes 1:

  • Autoantibodies (ANA, SMA ≥1:40 or ≥1:80, anti-LKM1 ≥1:40, or anti-SLA positive)
  • IgG levels (>upper limit of normal or >1.1× upper limit)
  • Liver histology (compatible with or typical of AIH)
  • Absence of viral hepatitis
  • ≥6 points: probable AIH; ≥7 points: definite AIH

• Comprehensive Diagnostic Criteria include additional parameters such as 1:

  • Female sex
  • ALP:AST (or ALT) ratio
  • Response to therapy
  • Other autoimmune diseases
  • Drug history and alcohol intake

Imaging Studies

• Ultrasound should be performed to assess liver morphology and exclude other causes of liver disease 1

• MR cholangiography should be performed in all children with AIH to exclude autoimmune sclerosing cholangitis 1

Monitoring Disease Activity

• Biochemical remission is defined as normalization of both transaminases and IgG levels 1, 3

• Combined ALT and IgG measurements provide the best non-invasive monitoring of disease activity - when both are normal, there is a 99% sensitivity for low inflammatory activity 3

• Caution: Normal serum parameters do not always indicate complete histological remission, but do identify patients at lower risk of fibrosis progression 3

Common Pitfalls to Avoid

• Overlooking AIH in viral hepatitis-endemic areas: AIH can coexist with viral hepatitis, particularly in regions with high prevalence of viral hepatitis 1

• Relying solely on autoantibody testing: About 10% of AIH cases may be seronegative initially; repeated testing may be necessary 1

• Missing AIH with normal IgG levels: Some patients, especially those with acute presentation, may have normal IgG levels 1

• Failure to obtain liver biopsy: Histology is essential for diagnosis, staging, and treatment decisions 1, 2