What is the initial treatment regimen for autoimmune hepatitis, including medications and dosages?

Initial Treatment for Autoimmune Hepatitis

The preferred initial treatment regimen is combination therapy with prednisone 30 mg daily plus azathioprine 50 mg daily (or 1-2 mg/kg/day), tapering prednisone to 10 mg daily over 4 weeks while maintaining azathioprine at the same dose. 1, 2, 3

Why Combination Therapy is Superior

Combination therapy produces significantly fewer corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44%) while maintaining equivalent efficacy. 1, 2, 3 This makes it the clear first choice for most patients with autoimmune hepatitis.

Specific Dosing Schedule

The standard induction regimen follows this timeline: 1, 2

• Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe)
• Week 2: Prednisone 20 mg/day + Azathioprine (same dose)
• Week 3: Prednisone 15 mg/day + Azathioprine (same dose)
• Week 4 onward: Prednisone 10 mg/day + Azathioprine (same dose) for maintenance

When to Use Prednisone Monotherapy Instead

Use prednisone alone (60 mg daily initially) only in specific situations: 1, 3

• Severe pre-treatment cytopenia (white blood cell count <2.5 × 10⁹/L or platelet count <50 × 10⁹/L)
• Pregnancy
• Complete thiopurine methyltransferase (TPMT) deficiency
• Known malignancy

Pre-Treatment Considerations

Measure TPMT activity before starting azathioprine to exclude homozygote TPMT deficiency, particularly in patients with pre-existing leucopenia. 3 This prevents potentially life-threatening myelosuppression.

Alternative for Non-Cirrhotic Patients with High Steroid Risk

Budesonide 9 mg daily plus azathioprine may be considered specifically in treatment-naive, non-cirrhotic patients with severe steroid-related side effects such as psychosis, poorly controlled diabetes, or severe osteoporosis. 1, 4 However, this is not appropriate for cirrhotic patients due to impaired first-pass metabolism. 1

Monitoring Schedule

• Assess treatment response at 4-8 weeks after initiation, with serum aminotransferase levels typically improving within 2 weeks 2, 3
• Monitor serum aminotransferase levels monthly, as small decrements in prednisone dose can trigger marked increases in aminotransferase levels 2, 3
• Monitor complete blood count regularly for azathioprine-related myelosuppression 1

Treatment Duration and Goals

Continue treatment for at least 2 years and for at least 12 months after normalization of liver enzymes. 2, 3, 4 The average duration to achieve normal liver tests is 19 months, with histological resolution requiring an additional 3-8 months. 1

Complete normalization of both transaminases AND IgG levels should be the goal, as persistent elevations predict relapse, ongoing histological activity, and progression to cirrhosis. 4

Mandatory Prophylaxis Against Complications

All patients must receive from treatment initiation: 2, 3, 4

• Calcium and vitamin D supplementation
• DEXA scanning for bone mineral density monitoring at 1-2 year intervals
• Vaccination against hepatitis A and B early in susceptible patients

This prevents severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) that typically develop after 18 months of therapy at prednisone doses >10 mg daily. 2

Management of Non-Response

For confirmed non-responders, increase to high-dose therapy with either prednisone 60 mg daily alone or prednisone 30 mg daily plus azathioprine 150 mg daily (up to 2 mg/kg/day), continued for at least 1 month. 1, 2, 3 Clinical and laboratory findings resolve in 70% of patients treated with this high-dose regimen. 1

Common Pitfalls to Avoid

• Do not start azathioprine in patients with severe cytopenia (white blood cell <2.5 × 10⁹/L or platelets <50 × 10⁹/L) without TPMT testing 1, 3
• Do not use budesonide in cirrhotic patients due to impaired hepatic metabolism and risk of portal vein thrombosis 1
• Do not discontinue therapy based on laboratory normalization alone—histological resolution lags behind by 3-8 months 1
• Do not use prednisone monotherapy as first-line unless contraindications to azathioprine exist, as it causes 4-fold higher side effect rates 1

Expected Outcomes

80-90% of patients achieve biochemical improvement with transaminases normalizing within 6 months in most responders. 4 However, relapse occurs in 50-90% of patients within 12 months of stopping treatment, necessitating long-term maintenance therapy in many cases. 2, 4