What is the treatment plan for a patient with autoimmune hepatitis?

Treatment Plan for Autoimmune Hepatitis

First-Line Treatment: Combination Immunosuppression

All patients with active autoimmune hepatitis (AIH) must receive treatment with prednisolone plus azathioprine, which achieves remission in 80-90% of patients and provides proven survival benefit. 1, 2, 3

Initial Dosing Regimen

• Prednisolone: Start at 30 mg/day (or up to 60 mg/day for more severe disease), then taper to 10 mg/day over 4 weeks 1, 2
• Azathioprine: Initiate at 50 mg/day when bilirubin is below 6 mg/dL, ideally two weeks after starting steroids, then increase to maintenance dose of 1-2 mg/kg/day based on response and toxicity 1, 2, 3

This combination regimen produces dramatically fewer corticosteroid-related side effects (10% versus 44%) compared to prednisone monotherapy. 2

Alternative First-Line Option

• Prednisone monotherapy: Start at 60 mg daily, taper to 40 mg, 30 mg, then maintain at 20 mg until endpoint—reserved for patients with cytopenia, pregnancy, thiopurine methyltransferase (TPMT) deficiency, or malignancy 2
• Budesonide 9 mg/day plus azathioprine: Consider for non-cirrhotic patients at high risk for steroid side effects, but never use budesonide in cirrhotic patients due to risk of systemic side effects from impaired first-pass metabolism 1, 2, 3

Treatment Goals and Monitoring

The therapeutic endpoint is complete normalization of both ALT and IgG levels—not just improvement, but complete normalization. 3

• Serum aminotransferase levels should improve within 2 weeks of starting therapy 2
• Persistent elevation of AST or ALT during treatment predicts 3-11 times higher risk of relapse, ongoing histological activity, progression to cirrhosis, and hepatocellular carcinoma 4, 3
• Continue treatment for a minimum of 2 years before considering withdrawal 2, 3
• Liver biopsy before treatment termination is recommended, as 46% of patients with biochemical response for >6 months still have histological activity with Ishak score ≥4, which independently predicts death or liver transplantation 4

Maintenance Phase

Once remission is achieved:

• Reduce prednisolone to 7.5 mg/day when aminotransferases normalize 3
• After 3 months, taper to 5 mg/day 3
• Maintain azathioprine at 1-2 mg/kg as steroid-sparing agent 3

Management of Treatment Failure or Intolerance

Step 1: Reassess Diagnosis and Adherence

Failure of adequate response should prompt reconsideration of diagnosis or evaluation of treatment adherence, as non-adherence is a major cause of relapse, particularly in adolescents and young adults. 1, 3

Step 2: Optimize First-Line Therapy

For confirmed diagnosis with adherence but suboptimal response:

• Increase dosage of prednisolone and azathioprine 1
• Consider long-term low-dose corticosteroid therapy with gradual decrease to 10 mg daily 2

Step 3: Second-Line Agents

Mycophenolate mofetil (MMF) is the preferred second-line agent, particularly for azathioprine intolerance rather than refractory disease. 2, 3

• MMF dosing: Start at 1 g daily, increase to maintenance of 1.5-2 g daily 2, 3
• Efficacy: 58% response in azathioprine intolerance versus only 23% in refractory disease 3
• Critical warning: MMF is absolutely contraindicated in pregnancy (Category D) due to severe cranial, facial, and cardiac abnormalities 3

Tacrolimus may be more effective for refractory disease not responding to standard therapy. 2

• Tacrolimus dosing: Start at 0.075 mg/kg daily, adjust to maintenance of 1 mg daily to 3 mg twice daily, targeting trough level of 0.6-1.0 ng/mL 4, 2
• Cyclosporine (2-5 mg/kg daily, target trough 100-300 ng/mL) has shown effectiveness, particularly in pediatric patients 4, 2

Special Clinical Situations

Acute Severe AIH

Treat with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 1, 3

• If no improvement within 7 days, evaluate for liver transplantation 2, 3

AIH-PBC Overlap Syndrome

Combined therapy with ursodeoxycholic acid (UDCA) 13-15 mg/kg/day plus immunosuppressants is required, with treatment directed at the predominant disease component. 1, 3

Pregnancy

• Azathioprine requires risk-benefit analysis but may be continued if disease control requires it 3
• MMF is absolutely contraindicated 3

Critical Safety Monitoring and Pitfalls

Before Starting Azathioprine

Check TPMT levels to exclude homozygote deficiency, especially in patients with pre-existing leucopenia. 1, 2, 3

• Azathioprine hepatotoxicity is more common in patients with advanced liver disease 1
• Discontinue azathioprine immediately if intolerance symptoms emerge 3

Corticosteroid Toxicity

• Cosmetic side effects occur in 80% of patients after 2 years of treatment 2
• Severe side effects typically develop after 18 months at prednisone doses >10 mg daily 2

Monitoring During Treatment

• Regular monitoring of immunosuppressant drug levels is indicated to assess adherence 3
• Transient elastography should be performed after hepatic inflammation has been resolved in patients undergoing induction therapy to assess fibrosis 4

Treatment Withdrawal

Never withdraw therapy in any patient who has not achieved complete normalization of biochemistry, as this reduces the relative risk of relapse by 3-fold to 11-fold. 2, 5

• Treatment withdrawal is achievable in less than 20% of patients after 2 years of sustained remission 6
• Liver biopsy may show persistent interface hepatitis in 55% of patients with normal serum enzymes, highlighting the importance of histological assessment before treatment withdrawal 2