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 and azathioprine at 1-2 mg/kg/day. 1
Treatment Regimen Details
The European Association for the Study of the Liver recommends the following specific dosing schedule:
- Initial prednisolone dose: 30-60 mg/day
- Azathioprine: Start at 50 mg/day, then increase to maintenance dose of 1-2 mg/kg/day
- Monitoring: Weekly liver tests and blood counts for 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 |
Patient Selection Considerations
Treatment should be initiated for:
- Patients with incapacitating symptoms (fatigue, arthralgia)
- Those with severe laboratory abnormalities
- Patients with bridging necrosis or multilobular necrosis on histology 1, 2
Treatment Efficacy and Outcomes
- The combination regimen achieves remission in approximately 80% of patients within 3 years 3
- 10-year and 20-year survival rates exceed 80% with appropriate treatment 3
- Untreated patients with severe disease have a high mortality rate (60% at 6 months) 1
- Better efficacy has been demonstrated when using a combination of prednisone and azathioprine from the beginning of treatment rather than introducing azathioprine later 4
Alternative First-Line Options
- Budesonide combined with azathioprine may be considered for non-cirrhotic patients with uncomplicated disease 5
- Important caveat: Budesonide is contraindicated in cirrhotic patients or those with portosystemic shunts due to its 90% first-pass hepatic clearance 1
Monitoring Treatment Response
- Serum aspartate aminotransferase (AST/ALT) and gamma-globulin/IgG levels are the most useful indices to monitor during therapy 1, 2
- Treatment goals include:
- Complete biochemical remission (normalization of both serum aminotransferase and IgG levels)
- Histological resolution of inflammation 1
- Liver biopsy is recommended before termination of immunosuppressive treatment to confirm histological remission 1
Important Precautions and Adjunctive Care
- All patients on steroids should receive calcium (1,000-1,200 mg daily) and vitamin D (400-800 IU daily) supplementation to prevent osteoporosis 1
- Assess bone density at baseline in patients with risk factors for osteoporosis
- Evaluate metabolic syndrome components before starting glucocorticoid therapy 1
- Consider vaccination against hepatitis A and B for susceptible patients 1
Second-Line Therapy Options
If patients fail to respond to standard therapy or develop significant side effects:
- Mycophenolate mofetil (MMF) is the preferred initial second-line agent, especially for azathioprine intolerance 1
- Tacrolimus is an alternative second-line agent (56% remission rate) 1, 6
- Cyclosporine may be considered as salvage therapy 1, 6
Special Considerations
- Pregnant patients: Azathioprine should be discontinued if possible during pregnancy (FDA pregnancy category D) 1
- Elderly patients: Combination therapy is preferred due to lower incidence of corticosteroid-related complications 2
- Patients with severe pre-existing comorbidities (vertebral compression, psychosis, brittle diabetes, uncontrolled hypertension) require careful evaluation before starting treatment 1
- Patients with severe pre-treatment cytopenia should avoid azathioprine 1