From the Guidelines
Azathioprine is used in acute autoimmune hepatitis as an immunosuppressive steroid-sparing agent, typically prescribed alongside corticosteroids to allow for eventual steroid dose reduction, with the standard dosing being 1-2 mg/kg/day, often starting at 50 mg daily and gradually increasing while monitoring for side effects 1.
Purpose of Azathioprine
The primary purpose of azathioprine in the treatment of acute autoimmune hepatitis is to reduce the proliferation of T and B lymphocytes involved in the autoimmune attack on hepatocytes, thereby minimizing steroid exposure and associated complications.
Dosage and Administration
The standard dosing of azathioprine is 1-2 mg/kg/day, often starting at 50 mg daily and gradually increasing while monitoring for side effects 1.
Mechanism of Action
Azathioprine works by inhibiting purine synthesis, which reduces the proliferation of T and B lymphocytes involved in the autoimmune attack on hepatocytes.
Monitoring and Side Effects
Before starting azathioprine, patients should have thiopurine methyltransferase (TPMT) activity testing to identify those at risk for severe bone marrow suppression 1. Regular monitoring of complete blood counts and liver function tests is essential during treatment. Common side effects include nausea, vomiting, bone marrow suppression, and increased risk of infections.
Treatment Duration
Azathioprine typically requires 3-6 months to achieve its full therapeutic effect, so corticosteroids remain the primary initial treatment for controlling acute inflammation in autoimmune hepatitis 1.
Key Considerations
- Azathioprine is not used alone for initial treatment of acute disease but is added to the regimen to maintain remission while minimizing steroid exposure and associated complications.
- The combination of prednisolone and azathioprine has been shown to be effective in improving serum liver tests, liver histology, and survival in patients with autoimmune hepatitis 1.
- Patients should receive calcium and vitamin D supplementation, and bone DEXA scanning should be performed at 1-2-yearly intervals while on steroids, with osteopenia and osteoporosis actively treated 1.
From the FDA Drug Label
Azathioprine suppresses disease manifestations as well as underlying pathology in animal models of autoimmune disease For example, the severity of adjuvant arthritis is reduced by azathioprine. The mechanisms whereby azathioprine affects autoimmune diseases are not known. Azathioprine is immunosuppressive, delayed hypersensitivity and cellular cytotoxicity tests being suppressed to a greater degree than are antibody responses
The purpose of azathioprine in the treatment of acute autoimmune hepatitis is to suppress the immune system and reduce disease manifestations.
- Azathioprine has been shown to be immunosuppressive in animal models of autoimmune disease.
- The exact mechanisms of azathioprine in autoimmune diseases are not known. 2
From the Research
Purpose of Azathioprine in Acute Autoimmune Hepatitis
The purpose of azathioprine in the treatment of acute autoimmune hepatitis is to:
- Induce and maintain remission in patients with autoimmune hepatitis (AIH) 3, 4, 5, 6
- Reduce the frequency of corticosteroid-related side effects when used in combination with prednisone 3, 5, 6
- Serve as a sole agent to maintain remission in patients who have achieved remission 3, 4
Treatment Regimens
Azathioprine can be used in the following treatment regimens:
- As a combination therapy with prednisone to induce and maintain remission 3, 5, 6
- As a monotherapy to maintain remission in patients who have achieved remission 4
- As a maintenance therapy with low dosages to prevent relapse in patients who have relapsed repeatedly 3, 6
Benefits and Considerations
The use of azathioprine in the treatment of acute autoimmune hepatitis has several benefits and considerations:
- Azathioprine monotherapy is equivalent to dual therapy with prednisone and azathioprine in maintaining remission 4
- Azathioprine can mitigate the risks of long-term corticosteroid therapy 4
- Proper patient selection, effective pre-treatment counseling, and individualized dosing schedules can reduce complications associated with azathioprine therapy 7