What is the initial treatment for autoimmune hepatitis?

Initial Treatment for Autoimmune Hepatitis

The initial treatment for autoimmune hepatitis should be a combination of prednisone (or prednisolone) plus azathioprine, as this regimen is associated with fewer corticosteroid-related side effects than prednisone monotherapy (10% versus 44%). 1

Standard Treatment Regimens for Adults

Combination Therapy (Preferred Approach)

• Prednisone 30 mg/day initially (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day 1
• This regimen should be continued for at least 2 years and for at least 12 months after normalization of transaminases 1
• The combination approach is preferred due to significantly fewer steroid-related side effects compared to prednisone monotherapy 1

Prednisone Monotherapy (Alternative Approach)

• Used when azathioprine is contraindicated (e.g., severe cytopenia, TPMT deficiency) 1
• Initial dose: 60 mg/day, reducing over 4 weeks to 20 mg/day 1
• Maintenance dose: 20 mg/day and below 1
• Higher rate of steroid-related side effects (44% versus 10% with combination therapy) 1

Dosing Schedule for Combination Therapy

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

Monitoring Response

• Assess response by 4-8 weeks after treatment initiation 1
• If positive biochemical response is observed, taper prednisone to 5-10 mg daily over the next 6 months while maintaining azathioprine 1
• Laboratory testing should be performed every 2-4 weeks initially, then every 3-4 months once biochemical remission is achieved 1

Special Considerations

For Patients with Cytopenia

• Consider measuring thiopurine methyltransferase (TPMT) activity before starting azathioprine to exclude homozygote TPMT deficiency 1
• Prednisone monotherapy is appropriate for patients with severe pre-treatment cytopenia (WBC <2.5×10^9/L or platelets <50) 1

For Non-Responding Patients

• Consider higher doses of steroids combined with azathioprine 2 mg/kg/day 1
• Alternative options include tacrolimus or cyclosporine for steroid-refractory cases 1

For Patients with Steroid Intolerance

• Budesonide may be an alternative to prednisone in non-cirrhotic patients 1
• Mycophenolate mofetil can be used in patients intolerant to azathioprine 1

Treatment Endpoints and Long-Term Management

• Treatment should continue until remission, which is defined as normal laboratory indices (AST/ALT, γ-globulin, IgG) and resolution of liver inflammation on biopsy 1
• Average duration of initial treatment is 18-24 months 1
• Liver biopsy prior to treatment termination is the only method to ensure full resolution of disease 1
• Relapse occurs in 50-90% of patients within 12 months of stopping treatment 1, 2
• After relapse, consider long-term maintenance with azathioprine 2 mg/kg/day 1, 2

Prevention of Treatment Complications

• All patients should receive calcium and vitamin D supplementation 1
• Bone mineral density should be monitored with DEXA scanning at 1-2 year intervals 1
• Vaccination against hepatitis A and B should be performed early in susceptible patients 1

Remember that early and appropriate treatment significantly improves outcomes by reducing progression to cirrhosis and liver-related mortality 1, 3.