What is the workup for autoimmune hepatitis?

Autoimmune Hepatitis Workup

The workup for autoimmune hepatitis (AIH) requires a combination of laboratory tests, immunological markers, and liver biopsy, with liver biopsy being essential for definitive diagnosis as it cannot be diagnosed without compatible histological findings. 1

Initial Laboratory Evaluation

Basic Laboratory Tests

• Liver function tests
  • Serum aminotransferases (AST/ALT) - typically markedly elevated
  • Alkaline phosphatase (ALP) - normal or mildly elevated
  • Bilirubin - may be elevated
  • ALP:AST (or ALT) ratio <1.5 is suggestive of AIH 2
• Serum immunoglobulin G (IgG) - elevated in 90% of cases 1, 2
  • Note: IgG may be normal in 10% of patients, especially in acute presentations (25-39%) 1
• Complete blood count
• Coagulation profile

Autoantibody Testing

• First-line autoantibody testing by indirect immunofluorescence (IFA) 1:

  • Antinuclear antibodies (ANA) - present in 75-95% of AIH-1
  • Smooth muscle antibodies (SMA) - present in up to 75% of AIH-1
  • Anti-liver kidney microsome type 1 (anti-LKM1) - present in 70% of AIH-2
  • Anti-liver cytosol type 1 (anti-LC1) - present in 30% of AIH-2

• Second-line autoantibody testing (if initial tests negative but AIH still suspected) 1, 2:

  • Anti-soluble liver antigen (anti-SLA) - specific for AIH, present in 20-30% of cases
  • Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) - may be the only marker in some AIH-1 cases
  • Additional specialized testing: anti-F-actin, anti-Ro52

Important Considerations for Autoantibody Testing

• Significant titers in adults are ≥1:40 by immunofluorescence 2
• HEp-2 cells should be used for ANA testing 1
• Rodent tissues should be used for SMA testing 1
• Testing should include kidney, liver, and stomach sections to detect all relevant reactivities 3
• Anti-LKM1 can be confused with anti-mitochondrial antibody (AMA) if only rodent kidney is used 3

Exclusion of Other Liver Diseases

• Viral hepatitis markers (HBV, HCV, HAV, HEV)
• Drug history (to exclude drug-induced liver injury)
• Alcohol intake assessment
• Tests for metabolic liver diseases:
  • Wilson's disease (ceruloplasmin, 24-hour urinary copper)
  • Hereditary hemochromatosis (iron studies)
  • Alpha-1 antitrypsin deficiency
• Tests for other autoimmune liver diseases:
  • Anti-mitochondrial antibody (AMA) for primary biliary cholangitis
  • Radiologic imaging studies to exclude biliary obstruction or primary sclerosing cholangitis

Liver Biopsy

• Essential for definitive diagnosis 1, 2
• Key histological features to look for:
  • Interface hepatitis
  • Predominantly lymphoplasmacytic infiltrate
  • Hepatocyte rosettes
  • Absence of biliary lesions or granulomas
  • Absence of other specific features suggesting alternative diagnoses

Diagnostic Scoring Systems

Two validated scoring systems can help establish the diagnosis 2:

1. Original Revised Scoring System (1999):

   • Score ≥15: Definite AIH
   • Score 10-15: Probable AIH

2. Simplified Scoring System (2008):

   • Score ≥7: Definite AIH
   • Score ≥6: Probable AIH

Diagnostic Algorithm

1. Initial evaluation for liver disease of unknown etiology:

   • Test for ANA, SMA, and serum IgG level
   • Rule out other etiologies with appropriate tests

2. If ANA/SMA positive and/or serum IgG elevated:

   • Proceed to liver biopsy

3. If ANA/SMA negative but AIH still suspected:

   • Test for anti-LKM1, anti-LC1, anti-SLA, and p-ANCA
   • If any positive, proceed to liver biopsy
   • If all negative, consider alternative diagnoses or seronegative AIH

4. If histology is compatible with AIH:

   • Apply diagnostic scoring systems
   • Consider induction therapy

5. If histology is equivocal but AIH still suspected:

   • Consider steroid trial for seronegative AIH 1

Special Considerations

• In children, all AIH patients should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 2
• About 10-20% of patients may have insufficient response to standard therapy 2
• Approximately 1/3 of adult patients and 1/2 of children present with cirrhosis at diagnosis 2
• Extra-hepatic autoimmune diseases are common in AIH patients 2

Remember that the clinical presentation of AIH is highly variable, and the diagnosis requires careful exclusion of other causes of liver disease together with a suggestive pattern of clinical and laboratory abnormalities 4.