Initial Treatment for Autoimmune Hepatitis
The 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 (30-60 mg/day) and azathioprine at 50 mg/day initially, increasing to 1-2 mg/kg/day maintenance dose. 1
Standard Treatment Regimen
Initial Therapy
- Prednisolone: 30-60 mg/day initially
- Azathioprine: Start at 50 mg/day, then increase to 1-2 mg/kg/day maintenance dose
- Weekly liver tests and blood counts for the first 4 weeks, then monthly once stable
Recommended Tapering Schedule (for a 60 kg patient)
| 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 |
Alternative First-Line Options
For patients without cirrhosis, severe acute hepatitis, or acute liver failure:
- Budesonide (9 mg/day) + azathioprine can be considered 1
- Advantage: 90% first-pass hepatic clearance, reducing systemic steroid side effects
- Contraindication: Cirrhotic patients or those with portosystemic shunts
Prednisolone Monotherapy (60 mg/day initially)
Appropriate in specific scenarios:
- Patients with cytopenia who cannot tolerate azathioprine
- Pregnant patients (azathioprine has FDA pregnancy category D rating) 2
- Patients with thiopurine methyltransferase (TPMT) deficiency 2, 1
Treatment Monitoring and Endpoints
Key Monitoring Parameters
- Serum AST/ALT levels
- Total bilirubin
- Gamma-globulin levels
- Complete blood count (especially with azathioprine)
Treatment Endpoints 2
- Remission: Disappearance of symptoms, normal serum aminotransferases, bilirubin and gamma-globulin levels, normal hepatic tissue or inactive cirrhosis
- Treatment failure: Worsening clinical, laboratory, and histological features despite compliance with therapy
- Incomplete response: Some or no improvement after 2-3 years of compliant therapy
- Drug toxicity: Development of intolerable side effects
Special Considerations
Azathioprine Considerations
- Blood thiopurine methyltransferase (TPMT) activity should be assessed in patients with pre-existing cytopenia or those who develop cytopenia during therapy 2
- Only 0.3-0.5% of the population has severe TPMT deficiency, but these patients are at high risk for myelosuppression 2
Pregnancy Considerations
- Azathioprine should be discontinued if possible during pregnancy 2
- Postpartum exacerbation of AIH is common; resume standard therapy 2 weeks prior to anticipated delivery 2
- Monitor serum AST/ALT levels at 3-week intervals for at least 3 months after delivery 2
Steroid-Related Complications
- Calcium and vitamin D supplementation for all patients on steroids
- DEXA scanning at 1-2 year intervals
- Monitor for hypertension, diabetes, and emotional instability
Second-Line Options for Non-Responders or Intolerant Patients
If standard therapy fails or causes intolerance:
- Mycophenolate mofetil (MMF): First choice for azathioprine intolerance (58% response rate) 1
- Tacrolimus: Alternative for non-responders (56% remission rate) 1
- Cyclosporine: Considered as salvage therapy 1
Important Clinical Pitfalls
Relapse risk: 50-90% of patients relapse within 12 months of stopping treatment 1
- Reintroduction of initial regimen usually achieves biochemical remission again
Incomplete assessment of remission:
- Normal serum AST and gamma-globulin levels do not guarantee histological resolution
- Interface hepatitis is found in 55% of patients with normal laboratory values 1
- Consider liver biopsy before terminating immunosuppressive treatment
Transplant referral timing:
- Consider referral for patients with decompensation at presentation, severe disease with poor response, fulminant hepatic failure, or high MELD/Child-Pugh scores 1
The combination of prednisolone and azathioprine remains the cornerstone of AIH treatment, with strong evidence supporting its efficacy in achieving remission in 80% of patients and improving long-term survival rates to over 80% 3, 4.