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 approach:
- 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 1: Prednisolone 60 mg/day
- Week 2: Prednisolone 50 mg/day
- Week 3: Prednisolone 40 mg/day + Azathioprine 50 mg/day
- Week 4: Prednisolone 30 mg/day + Azathioprine 50 mg/day
- Week 5: Prednisolone 25 mg/day + Azathioprine 100 mg/day
- Week 6: Prednisolone 20 mg/day + Azathioprine 100 mg/day
- Weeks 7-8: Prednisolone 15 mg/day + Azathioprine 100 mg/day
- Weeks 9-10: Prednisolone 12.5 mg/day + Azathioprine 100 mg/day
- Beyond Week 10: Prednisolone 10 mg/day + Azathioprine 100 mg/day 1
Evidence Supporting Combination Therapy
Research has consistently shown that combination therapy is superior to monotherapy:
- Better efficacy is achieved in the induction phase using a combination of prednisone and azathioprine from the beginning of treatment 2
- The combination regimen is preferred, especially in elderly patients, due to lower incidence of corticosteroid-related complications 3
- Combination therapy can achieve remission in 80% of patients within 3 years, with 10-year and 20-year survival rates exceeding 80% 4
Patient Selection for Treatment
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, 3
Important Considerations and Precautions
Contraindications and Special Populations
- Avoid azathioprine in patients with severe pre-treatment cytopenia
- Discontinue azathioprine if possible during pregnancy (FDA pregnancy category D)
- Budesonide is contraindicated in cirrhotic patients or those with portosystemic shunts 1
Prevention of Complications
- All patients on steroids should receive calcium (1,000-1,200 mg daily) and vitamin D (400-800 IU daily) supplementation to prevent osteoporosis
- Consider vaccination against hepatitis A and B for susceptible patients
- Monitor for HBV reactivation in HBsAg-negative/anti-HBc-positive patients 1
Monitoring Treatment Response
- Monitor serum aspartate aminotransferase and gamma-globulin levels as the most useful indices during therapy 3
- Complete biochemical remission (normalization of both serum aminotransferase and IgG levels) is the treatment goal
- Liver biopsy is recommended before termination of immunosuppressive treatment to confirm histological resolution 1
Alternative Therapies for Special Situations
If standard therapy fails or is contraindicated, consider:
- Mycophenolate mofetil (MMF) - preferred initial second-line agent, especially for azathioprine intolerance
- Tacrolimus - alternative second-line agent (56% remission rate in non-responders)
- Cyclosporine - may be considered as salvage therapy 1
Common Pitfalls to Avoid
- Failure to recognize relapse: Relapse occurs in 50-86% of patients after drug withdrawal 3
- Inadequate monitoring: Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy 1
- Overlooking comorbidities: Assess for metabolic syndrome components before starting glucocorticoid therapy 1
- Missing postpartum exacerbation: Monitor serum liver enzymes at 3-week intervals for at least 3 months after delivery 1