What is the workup and treatment for autoimmune hepatitis?

Autoimmune Hepatitis Workup and Treatment

The diagnosis of autoimmune hepatitis (AIH) requires a comprehensive laboratory workup, autoantibody testing, and liver biopsy, followed by immunosuppressive therapy with corticosteroids alone or in combination with azathioprine as first-line treatment. 1

Diagnostic Workup

Clinical and Laboratory Assessment

• Obtain complete medical, medication, alcohol, and hepatitis exposure history
• Initial laboratory testing should include:
  • Liver function tests (AST, ALT, ALP, bilirubin)
  • Serum immunoglobulin levels (particularly IgG)
  • Complete blood count
  • Prothrombin time/INR
• Look for elevated transaminases with ALP:AST ratio <1.5 2
• Hypergammaglobulinemia with IgG >1.5 times upper limit of normal is characteristic but not required for diagnosis 1, 2

Autoantibody Testing

• Test for conventional autoantibodies by indirect immunofluorescence 1:
  • Antinuclear antibodies (ANA)
  • Smooth muscle antibodies (SMA)
  • Anti-liver kidney microsome type 1 (anti-LKM1)
  • Anti-liver cytosol type 1 (anti-LC1)
• Significant titers in adults are ≥1:40 by immunofluorescence 1
• In children, titers of 1:20 for ANA/SMA and 1:10 for anti-LKM1 are significant 1
• Test for anti-soluble liver antigen/liver pancreas (anti-SLA/LP) by ELISA or immunoblotting when conventional antibodies are negative 1, 2

Exclusion of Other Liver Diseases

• Rule out viral hepatitis with serological testing for:
  • Hepatitis A, B, and C
• Exclude metabolic and genetic liver diseases:
  • Wilson's disease (ceruloplasmin, 24-hour urinary copper)
  • Alpha-1 antitrypsin deficiency (serum levels and phenotyping)
  • Hemochromatosis (iron studies)
• Rule out drug-induced liver injury and alcoholic liver disease 1, 2

Liver Biopsy

• Liver biopsy is essential for definitive diagnosis and should be performed unless contraindicated 1
• Key histological features to look for:
  • Interface hepatitis (hallmark finding)
  • Portal plasma cell infiltration
  • Emperipolesis (penetration of one cell into another)
  • Hepatocellular rosette formation
  • Absence of biliary lesions or granulomas 1, 2

Diagnostic Scoring Systems

• Two validated scoring systems can help establish diagnosis:
  1. Original Revised Scoring System (1999):
     • Pretreatment score ≥15: definite AIH
     • Pretreatment score 10-15: probable AIH
  2. Simplified Scoring System (2008):
     • ≥7 points: definite AIH
     • 6 points: probable AIH 2

Treatment

Indications for Treatment

• All patients with moderate to severe inflammation should receive treatment:
  • AST/ALT >5 times upper limit of normal
  • Serum globulins >2 times upper limit of normal
  • Liver biopsy showing confluent necrosis 1
• Consider treatment in milder cases if:
  • Patient has symptoms
  • Cirrhosis is present on biopsy
  • Patient is younger 1

First-Line Treatment

• Standard therapy consists of prednisone alone or in combination with azathioprine 3, 4
• Combination regimen is preferred due to fewer corticosteroid-related side effects 4
• Initial regimen options:
  1. Prednisone alone: 60 mg daily, tapered over 4 weeks to maintenance dose of 20 mg daily
  2. Combination therapy: Prednisone 30 mg daily with azathioprine 50 mg daily 4

Monitoring Treatment Response

• Monitor transaminases and IgG levels regularly
• Normalization of both transaminases and IgG levels is the marker of complete biochemical remission 1
• Follow patients in a designated liver clinic with regular laboratory monitoring 1
• Consider repeat liver biopsy before withdrawing treatment to ensure histological remission 4

Treatment of Refractory Cases

• For non-responders to standard therapy, consider alternative agents:
  • Budesonide
  • Mycophenolate mofetil
  • Cyclosporine
  • Tacrolimus
  • 6-mercaptopurine
  • Rituximab 3

Long-Term Management

• Most patients require lifelong maintenance therapy 5
• For patients with multiple relapses, consider low-dose prednisone or indefinite azathioprine therapy 4
• Perform surveillance for hepatocellular carcinoma with liver ultrasound every 6 months in cirrhotic patients 2

Special Considerations

• Acute or fulminant presentation occurs in up to 40% of cases 2
• IgG levels may be normal in 25-39% of acute presentations 2
• Children with AIH should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 2
• Consider testing for APECED syndrome in patients with AIH and multiple endocrine disorders 2

The management of AIH requires careful monitoring and individualized treatment adjustments based on response. Early diagnosis and prompt initiation of immunosuppressive therapy are crucial to prevent progression to cirrhosis and liver failure.