What is the initial treatment for autoimmune hepatitis?

Initial Treatment for Autoimmune Hepatitis

The standard first-line treatment for autoimmune hepatitis 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

Treatment Regimens

First-Line Therapy Options:

1. Monotherapy Option:

   • Prednisone or prednisolone alone (60 mg daily)
   • Initial high dose maintained for at least 1 month

2. Combination Therapy Option (Preferred):

   • Prednisone or prednisolone (30 mg daily) plus azathioprine (150 mg daily)
   • Preferred especially in elderly patients due to lower incidence of corticosteroid-related complications 2
   • Better efficacy has been demonstrated when combination therapy is initiated from the beginning of treatment 3

Dosing and Tapering Schedule:

For a 60 kg patient, the European Association for the Study of the Liver (EASL) recommends the following tapering schedule 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

Efficacy and Response Rates

• Clinical and laboratory findings resolve in 70% of patients treated with high-dose regimens 4
• 20-41% achieve histological improvement to normal or near normal within 2 years 4
• Complete biochemical response is defined as normalization of both serum transaminases and IgG below the upper limit of normal within 6 months of treatment 1

Important Considerations

Dose Optimization:

Recent research suggests that an initial prednisolone dose below 0.50 mg/kg/day may be as effective as higher doses while substantially decreasing unnecessary steroid exposure 5. This challenges the traditional high-dose approach and suggests that lower initial doses may be appropriate for some patients.

Monitoring:

• Serum liver enzyme levels (AST/ALT) and IgG should be monitored at 3-6 month intervals during treatment 1
• Weekly liver tests and blood counts for the first 4 weeks, then monthly once stable 1
• Liver biopsy is the best method for evaluating completeness of response 2

Adverse Effects and Prevention:

• Up to 25% of patients may develop side effects requiring withdrawal in about 10% of cases 1
• All patients on steroids should receive calcium (1,000-1,200 mg) and vitamin D (400-800 IU) supplementation daily to prevent osteoporosis 1
• Systematic screening for infection before and during treatment is recommended 1

Treatment Alternatives for Suboptimal Responses

For patients who fail conventional therapy or experience significant side effects:

1. Calcineurin Inhibitors:

   • Ciclosporin and tacrolimus are effective in 93-98% of refractory cases 1
   • Ciclosporin: 2-5 mg/kg daily initially
   • Tacrolimus: 0.075 mg/kg daily initially, then 1 mg daily to 3 mg twice daily for maintenance

2. Mycophenolate Mofetil:

   • Effective for azathioprine intolerance with a 58% response rate
   • Initial dose: 1 g daily, increasing to maintenance dose of 1.5-2 g daily 1

3. Budesonide:

   • Emerging as a frontline treatment, especially for non-cirrhotic patients with uncomplicated disease 6
   • Combined with azathioprine has shown better efficacy and safety than conventional prednisone-based regimens in treatment-naive patients 6

Long-Term Management

• Most patients enter remission, but relapse occurs in 50-86% after drug withdrawal 2
• Maintenance therapy with low doses of prednisone or azathioprine can be used long-term in patients who have relapsed repeatedly 2
• Azathioprine alone at 2 mg/kg/day can maintain remission in 83% of patients who have been in complete remission for at least one year with combination therapy 7

Special Considerations

• Patients with acute liver failure should be placed on the transplant list even while receiving corticosteroids 1
• Liver transplantation is reserved for patients who deteriorate despite compliance with therapy or have decompensated disease not responding to medical management 1