First-Line Therapy for Autoimmune Hepatitis
The first-line therapy for autoimmune hepatitis is a combination of prednisolone (or prednisone) and azathioprine, with prednisolone typically started at 0.5-1 mg/kg/day and azathioprine at 1-2 mg/kg/day. 1, 2
Initial Treatment Approach
Standard Combination Therapy
- Prednisolone/Prednisone: Start with 30-60 mg/day (0.5-1 mg/kg/day)
- Azathioprine: Add at 50 mg/day initially, increasing to 1-2 mg/kg/day maintenance dose 1, 2
Many experts recommend delaying the introduction of azathioprine by approximately 2 weeks after starting prednisolone. This approach helps resolve diagnostic uncertainties and avoids the dilemma of distinguishing between azathioprine-induced hepatotoxicity and primary non-response to therapy 1.
Recommended Tapering Schedule
The European Association for the Study of the Liver (EASL) recommends the following tapering schedule for a 60 kg patient 1:
| Week | Prednisolone (mg/day) | Azathioprine (mg/day) |
|---|---|---|
| 1 | 60 | - |
| 2 | 50 | - |
| 3 | 40 | 50 |
| 4 | 30 | 50 |
| 5 | 25 | 100* |
| 6 | 20 | 100* |
| 7-8 | 15 | 100* |
| 9-10 | 12.5 | 100* |
| >10 | 10 | 100* |
*Azathioprine dose should be 1-2 mg/kg according to body weight.
Alternative First-Line Options
Budesonide-Based Regimen
For patients without cirrhosis, severe acute hepatitis, or acute liver failure, budesonide (9 mg/day) in combination with azathioprine is an alternative first-line therapy 1, 2. This regimen may be preferred in patients at high risk for corticosteroid side effects 3.
Key considerations for budesonide:
- Has 90% first-pass hepatic clearance
- Contraindicated in cirrhotic patients or those with portosystemic shunts 1
- May normalize serum aminotransferases more effectively than traditional prednisolone (47% vs 18%) with fewer side effects (28% vs 53%) 1
Prednisolone Monotherapy
Prednisolone monotherapy (60 mg/day initially) is appropriate in certain scenarios:
- Patients with cytopenia who cannot tolerate azathioprine
- Pregnant patients (azathioprine can be continued, but some clinicians prefer to avoid it) 2
- Patients with thiopurine methyltransferase (TPMT) deficiency 1
Treatment Monitoring and Goals
Treatment Goals
- Complete biochemical remission (normalization of both serum aminotransferases and IgG levels) 2
- Histological resolution of inflammation 2
Monitoring Schedule
- Weekly liver tests and blood counts for the first 4 weeks
- Monthly monitoring once stable 2
- Clinical improvement should be evident within 2 weeks
- 80-90% of patients achieve laboratory remission within 6-12 months 2
Special Considerations
Cirrhotic Patients
- Standard prednisolone and azathioprine combination is preferred
- Avoid budesonide due to unpredictable systemic exposure 1
Severe Acute Disease
- Higher initial prednisolone doses (up to 1 mg/kg/day) may be used 2
- Consider early liver transplantation evaluation if no improvement within 2 weeks 1, 2
TPMT Testing
Testing for TPMT activity prior to azathioprine initiation is encouraged in all patients to identify those at risk for severe myelosuppression 1.
Treatment Duration and Relapse
- Minimum treatment duration of 24 months 2
- Consider liver biopsy after 2 years to confirm histological remission 2
- Relapse occurs in 50-86% of patients after drug withdrawal 2, 4
- For patients with multiple relapses, consider long-term maintenance therapy with azathioprine monotherapy (2 mg/kg/day) 2, 4
Second-Line Therapies
For patients who fail first-line therapy or develop intolerance:
- Mycophenolate mofetil (MMF): Preferred initial second-line agent, especially for azathioprine intolerance 1, 2
- Tacrolimus: Alternative second-line agent, more effective than MMF for non-responders (56% vs 34% remission rate) 2
- Cyclosporine: May be considered as a salvage therapy 1
The combination of prednisolone and azathioprine remains the cornerstone of autoimmune hepatitis treatment, with strong evidence supporting its efficacy in improving survival and preventing disease progression 5, 4.