Treatment of Autoimmune Hepatitis
The standard first-line treatment 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
First-Line Therapy
Combination Therapy (Preferred Approach)
- Initial prednisolone dose: 30-60 mg/day
- Initial azathioprine dose: 50 mg/day, increasing to 1-2 mg/kg/day maintenance dose
- Tapering schedule for a 60 kg patient as recommended by EASL 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 |
- The combination regimen is preferred, especially in elderly patients, due to lower incidence of corticosteroid-related complications 2
Alternative First-Line Options
For non-cirrhotic patients without severe acute hepatitis or liver failure: Budesonide (9 mg/day) plus azathioprine 1
- Budesonide has 90% first-pass hepatic clearance
- Contraindicated in cirrhotic patients or those with portosystemic shunts
Prednisolone monotherapy (60 mg/day initially) is appropriate in:
- Patients with cytopenia who cannot tolerate azathioprine
- Pregnant patients
- Patients with thiopurine methyltransferase (TPMT) deficiency 1
Monitoring and Treatment Duration
- Weekly liver tests and blood counts for first 4 weeks, then monthly monitoring once stable
- Clinical improvement should be evident within 2 weeks
- 80-90% of patients achieve laboratory remission within 6-12 months
- Minimum treatment duration is 24 months
- Consider liver biopsy after 2 years to confirm histological remission 1
Treatment Goals
- Complete biochemical remission (normalization of serum aminotransferases and IgG levels)
- Histological resolution of inflammation 1
- Important: Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy, highlighting the importance of liver biopsy in monitoring treatment response
Second-Line Therapy
For patients who are intolerant or non-responsive to standard therapy:
Mycophenolate mofetil (MMF) - preferred initial second-line agent, especially for azathioprine intolerance 1
- Note: MMF has a high rate of intolerance (34%), but achieves remission in 84% of those who tolerate it 3
Tacrolimus - alternative second-line agent
- More effective than MMF for non-responders (56% vs 34% remission rate) 1
Cyclosporine - may be considered as salvage therapy 1
Long-Term Maintenance
- After achieving remission, azathioprine alone at 2 mg/kg/day can maintain remission in approximately 83% of patients 4
- This approach helps avoid long-term corticosteroid side effects
Liver Transplantation
Consider referral for transplantation in patients with:
- Decompensation at presentation
- Severe disease with no/slow response to treatment
- Fulminant hepatic failure
- Clinical liver decompensation
- High MELD or Child-Pugh scores 1
Management of Side Effects
- Provide calcium and vitamin D supplementation to all patients on steroids
- Consider DEXA scanning at 1-2 year intervals
- Test for TPMT activity prior to azathioprine initiation to identify patients at risk for severe myelosuppression
- Monitor for common side effects of azathioprine, including arthralgia and myelosuppression 1, 4
Clinical Pearls and Pitfalls
- Pitfall: Discontinuing treatment too early. Most patients (50-79%) relapse after drug withdrawal 5
- Pitfall: Failing to recognize azathioprine toxicity. Watch for myelosuppression, particularly in patients with TPMT deficiency
- Pearl: Better efficacy is achieved using combination therapy from the beginning rather than starting with prednisone alone and adding immunosuppressants later 6
- Pearl: Absence of cirrhosis at presentation may predict eventual need for MMF therapy 3