Treatment of Autoimmune Hepatitis
Start combination therapy with prednisone (30 mg/day initially, tapering to 10 mg/day over 4 weeks) plus azathioprine (1-2 mg/kg/day) as first-line treatment for autoimmune hepatitis, as this regimen achieves remission in 80-90% of patients while causing significantly fewer corticosteroid-related side effects than prednisone monotherapy (10% vs 44%). 1, 2
Initial Treatment Strategy
Preferred regimen: Combination therapy from treatment initiation produces superior outcomes compared to sequential introduction of medications. 3
Standard Dosing Schedule
- Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe) 1, 2
- Week 2: Prednisone 20 mg/day + Azathioprine (same dose) 2
- Weeks 3-4: Prednisone 15 mg/day + Azathioprine (same dose) 2
- Maintenance: Prednisone 10 mg/day + Azathioprine (same dose) until remission 1, 2
Alternative Approach for Severe Hyperbilirubinemia
Start prednisone first, then add azathioprine after 2 weeks when bilirubin is below 6 mg/dL, as azathioprine hepatotoxicity risk increases in advanced liver disease. 2, 4
Treatment Goals and Monitoring
Complete normalization of BOTH serum aminotransferases AND IgG levels must be achieved, as persistent elevations predict relapse, ongoing histological activity, and progression to cirrhosis. 2
- Early response assessment: Check liver enzymes at 4-8 weeks; serum aminotransferases should improve within 2 weeks of starting therapy 1, 2
- Monthly monitoring: Small decrements in prednisone dose can cause marked increases in aminotransferases 1
- Time to remission: Most patients achieve biochemical remission within 6-12 months; average duration is 19 months 2
Treatment Duration
Continue therapy for at least 2 years and for at least 12 months after normalization of liver enzymes. 1, 2 Average duration of initial treatment is 18-24 months. 1, 2
Special Populations Requiring Modified Regimens
Patients with Cytopenia
Use prednisone monotherapy in patients with white blood cell counts <2.5 × 10⁹/L or platelet counts <50 × 10⁹/L. 4 Consider measuring thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency. 2, 5
Non-Cirrhotic Patients at High Risk for Steroid Side Effects
Budesonide 9 mg/day plus azathioprine may be used specifically in treatment-naive, non-cirrhotic patients with early-stage disease. 2 However, budesonide has 90% first-pass hepatic clearance and must never be used in cirrhotic patients due to risk of systemic side effects from impaired metabolism. 4, 5
Pregnant Patients
Use prednisone monotherapy during pregnancy, as azathioprine is associated with placental transfer and potential teratogenicity in animals, though clinical data in autoimmune hepatitis patients show no increased fetal risk. 4
Management of Acute Severe Autoimmune Hepatitis
Treat immediately with high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 2 If no improvement occurs within 7 days, list for emergency liver transplantation. 2
Treatment Failure and Refractory Disease
Definition of Treatment Failure
Inability to achieve remission after 3 years (incomplete response) or deterioration during therapy warrants alternative strategies. 6
High-Dose Salvage Therapy
For confirmed non-responders, increase to prednisone 60 mg daily alone OR prednisone 30 mg daily plus azathioprine 150 mg daily for at least 1 month. 1, 2 This achieves laboratory response in 70% and tissue response in 21-41% of patients. 4
Second-Line Immunosuppressive Agents
When standard therapy fails or is not tolerated:
Mycophenolate mofetil: Most effective for azathioprine intolerance (58% response rate) rather than refractory disease (23% response rate) 4. Start at 1 g daily, increase to maintenance of 1.5-2 g daily 4, 5. Mycophenolate produces biochemical and histologic improvement without significant hematologic complications. 7
Tacrolimus or cyclosporine: More effective for steroid-refractory cases; tacrolimus starting dose is 0.075 mg/kg daily 2, 5
Critical pitfall: Mycophenolate is category D in pregnancy and causes severe cranial, facial, and cardiac abnormalities in neonates. 4
Long-Term Maintenance and Relapse Management
Relapse occurs in 50-90% of patients within 12 months of stopping treatment, even after achieving complete biochemical and histological remission. 1, 2 Only 20-28% achieve sustained remission off therapy. 2
After First Relapse
Reinitiate combination therapy with prednisone and azathioprine. 1
After Multiple Relapses
Treat with long-term maintenance azathioprine 2 mg/kg/day alone after achieving remission and withdrawing prednisone. 1 This maintains remission in 87% of adult patients during median observation of 67 months, with 83% remaining in remission for median of 67 months (range 12-128 months). 8
Steroid withdrawal benefits: After prednisolone withdrawal on azathioprine maintenance, patients lose cushingoid facies and experience median weight loss of 6.4 kg. 8
Prevention of Treatment Complications
Bone Health
All patients must receive calcium and vitamin D supplementation. 1, 2 Monitor bone mineral density with DEXA scanning at 1-2 year intervals. 1, 2
Vaccination
Perform hepatitis A and B vaccination early in susceptible patients. 1, 2
Minimizing Steroid Toxicity
Reduce prednisolone to ≤10 mg/day for long-term maintenance, as severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop only after 18 months at doses >10 mg daily. 1, 5
Monitoring for Azathioprine Toxicity
Watch for myelosuppression (leukocytes <4000/mm³, platelets <150,000/mm³), which occurs in approximately 6% of patients. 4, 8 Lymphopenia develops in 57% of patients on 2 mg/kg/day for >2 years. 8 Azathioprine hepatotoxicity is more common in advanced liver disease. 4, 5