Initial Treatment for Autoimmune Hepatitis with Positive Antibodies
The first-line treatment for autoimmune hepatitis is prednisone (or prednisolone) started immediately, followed by the addition of azathioprine after two weeks once bilirubin is below 6 mg/dL. 1, 2
Standard Induction Regimen
Prednisone dosing:
- Start prednisone at 30-40 mg daily (or up to 60 mg daily in severe cases) 1
- Taper over 4-8 weeks to a maintenance dose of 10 mg daily 1
- The combination regimen with azathioprine is strongly preferred over prednisone monotherapy because it reduces corticosteroid-related side effects from 44% to 10% 1, 2
Azathioprine addition:
- Add azathioprine after 2 weeks of prednisone initiation, ideally when bilirubin is below 6 mg/dL (100 μmol/L) 1
- Start at 50 mg daily, then increase to maintenance dose of 1-2 mg/kg daily based on tolerance 1
- Consider measuring thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote deficiency, especially if pre-existing cytopenia is present 1
Absolute Indications for Treatment
Treatment must be initiated if any of the following are present 1, 2:
- Serum aminotransferases >10-fold upper limit of normal
- Serum aminotransferases >5-fold upper limit of normal with γ-globulin ≥2-fold upper limit of normal
- Histological features of bridging necrosis or multilobular necrosis
- Incapacitating symptoms
Special Situations Requiring Modified Approach
Acute severe autoimmune hepatitis:
- Administer high-dose intravenous corticosteroids (≥1 mg/kg) immediately 1, 2
- If no improvement within 7 days, list for emergency liver transplantation 1, 2
Prednisone monotherapy (without azathioprine) is appropriate only for: 1
- Severe cytopenia (WBC <2.5 × 10⁹/L or platelets <50 × 10⁹/L)
- Pregnancy or contemplating pregnancy
- Short treatment trials (≤6 months)
- TPMT deficiency
Non-cirrhotic patients with anticipated severe steroid side effects:
- Consider budesonide 9 mg daily plus azathioprine as an alternative to prednisone 1
- Critical caveat: Budesonide should never be used in cirrhotic patients due to impaired first-pass metabolism and risk of systemic side effects 1
Monitoring Treatment Response
Expected timeline: 2
- Serum aminotransferases should improve within 2 weeks
- 80-90% of patients achieve normalization of transaminases within 6 months 1
- Complete normalization of both transaminases and IgG levels should be the treatment goal 1, 2
If inadequate response occurs:
- First reconsider the diagnosis and assess treatment adherence 1
- Increase prednisone to 60 mg daily or prednisone 30 mg daily with azathioprine 150 mg daily 1
- Consider referral to a transplant center if MELD score does not improve rapidly 1
Critical Pitfalls to Avoid
Do not delay azathioprine addition beyond 2 weeks if bilirubin permits, as this unnecessarily prolongs high-dose corticosteroid exposure 1
Do not use budesonide in cirrhotic patients - the 90% first-pass hepatic clearance is compromised in cirrhosis, leading to systemic corticosteroid effects without the intended safety benefit 1
Do not start azathioprine if severe cytopenia is present (WBC <2.5 × 10⁹/L or platelets <50 × 10⁹/L) without first measuring TPMT activity 1
Do not accept persistent transaminase elevation - this predicts relapse after treatment withdrawal, ongoing histological activity, progression to cirrhosis, and poor outcomes 1, 2
Supportive Measures
All patients on corticosteroids require 1:
- Calcium and vitamin D supplementation
- Baseline bone mineral densitometry of lumbar spine and hip
- Annual DEXA scanning while on steroids
- Active treatment of osteopenia/osteoporosis with bisphosphonates if indicated