Treatment for Autoimmune Hepatitis
The standard first-line treatment for autoimmune hepatitis (AIH) is prednisolone (0.5-1 mg/kg/day) alone or in combination with azathioprine (1-2 mg/kg/day), which can induce biochemical remission in up to 90% of patients within 12 months. 1, 2
First-Line Treatment Regimen
Initial Therapy
Prednisolone/Prednisone:
- Starting dose: 30-60 mg/day
- Gradually tapered according to response
Combination Therapy (preferred approach):
- Prednisolone/Prednisone as above
- Azathioprine: Start at 50 mg/day, increase to maintenance dose of 1-2 mg/kg/day 2
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 |
Monitoring
- Weekly liver tests and blood counts for first 4 weeks
- Monthly once stable
- Complete biochemical response defined as normalization of both serum transaminases and IgG within 6 months 2
Second-Line Treatment Options
For patients who fail first-line therapy due to treatment failure, incomplete response, or drug intolerance:
Mycophenolate Mofetil (MMF)
- Dosage: Start at 1g daily, increase to 1.5-2g daily
- Preferred as initial second-line agent due to superior ease-of-use and side-effect profile 1
- Particularly effective for patients intolerant to azathioprine (92% remission rate) 1
Tacrolimus
- Superior to MMF for non-responders to standard therapy (56% vs 34% remission rate) 1, 2
- Requires monitoring of trough levels
- Consider when MMF fails, especially in patients who had nonresponse (rather than intolerance) to standard therapy 1
Other Alternatives
- Cyclosporine as salvage therapy
- Budesonide 9 mg/day plus azathioprine for non-cirrhotic patients with severe steroid-related side effects 2
- 6-mercaptopurine, cyclophosphamide, and methotrexate may be considered in refractory cases 2
Long-Term Maintenance Therapy
- Azathioprine 2 mg/kg/day can be used as sole maintenance therapy after remission is achieved 3
- Long-term maintenance is often necessary as relapse is common when treatment is stopped 4
- Low-dose prednisone (<10 mg daily, median 7.5 mg) may be used to maintain AST <3x ULN 2
Special Considerations
Adverse Effects Management
- Up to 25% of patients develop side effects, requiring withdrawal in about 10% of cases 2
- All patients on steroids should receive calcium (1,000-1,200 mg) and vitamin D (400-800 IU) supplementation 2
- Monitor for:
- Steroid complications: vertebral compression, hyperglycemia, sodium retention
- Azathioprine complications: myelosuppression, pancreatitis, arthralgias
Pregnancy Considerations
- Azathioprine should be discontinued if possible during pregnancy (FDA pregnancy category D) 2
- Monitor for postpartum exacerbation with serum liver enzyme levels at 3-week intervals for at least 3 months after delivery 2
Liver Transplantation
- Indicated for patients who deteriorate despite compliance with therapy or have decompensated disease 2
- Consider referral for transplantation in patients with:
- Decompensation at presentation
- Severe disease with no/slow response to treatment
- Fulminant hepatic failure
- High MELD or Child-Pugh scores
Treatment Success Metrics
- Complete biochemical remission: normalization of both serum aminotransferase and IgG levels
- Histological improvement: reduction in hepatic fibrosis in 53%-57% of patients 1
- Remission off therapy: achieved in 19%-40% of patients observed for at least 3 years 1
Common Pitfalls
- Failure to normalize both serum aminotransferase and IgG levels (incomplete biochemical response)
- Premature withdrawal of therapy leading to relapse
- Inadequate monitoring of drug side effects
- Failure to use azathioprine as maintenance therapy (associated with inferior outcomes) 1
- Failure to recognize when to switch to second-line agents in non-responders