What is the initial treatment for autoimmune hepatitis?

Initial Treatment for Autoimmune Hepatitis

The initial treatment for autoimmune hepatitis should be prednisone (or prednisolone) in combination with azathioprine, as this regimen is more effective and has fewer steroid-related side effects than prednisone monotherapy. 1

Standard First-Line Treatment Regimen

Adult Patients

• Combination therapy (preferred approach):

  • Prednisone/prednisolone: 30 mg/day initially, reducing to 10 mg/day over 4 weeks
  • Azathioprine: 50 mg/day (1-2 mg/kg/day) 1

• Tapering schedule for prednisone/prednisolone:

  • Week 1: 30 mg/day
  • Week 2: 20 mg/day
  • Week 3-4: 15 mg/day
  • Maintenance: 10 mg/day or lower 1

Children

• Prednisone: 1-2 mg/kg/day (up to 60 mg/day) for two weeks
• Azathioprine: 1-2 mg/kg/day
• Taper prednisone over 6-8 weeks to 0.1-0.2 mg/kg/day or 5 mg/day 1

Rationale for Combination Therapy

1. Reduced steroid-related side effects: Combination therapy has significantly lower occurrence of corticosteroid-related side effects (10%) compared to prednisone monotherapy (44%) 1
2. Equivalent efficacy: Both regimens are equally effective in inducing remission 1
3. Better long-term outcomes: Combination therapy from the beginning of treatment course shows better efficacy in the induction phase 2

Special Considerations

Monotherapy Indications

Prednisone alone (60 mg/day initially, tapering to 20 mg/day over 4 weeks) should be used in patients with:

• Severe cytopenia (white blood cell counts <2.5 × 10^9/L)
• Complete thrombocytopenia (<50 platelets)
• Thiopurine methyltransferase deficiency 1

Azathioprine Timing

• Initiate azathioprine when bilirubin levels are below 6 mg/dl (100 μmol/L)
• Ideally start two weeks after beginning steroid treatment 1
• Consider checking thiopurine methyltransferase (TPMT) activity in patients with pre-existing leukopenia 1

Budesonide Alternative

• Budesonide (9 mg/day) plus azathioprine may be considered in:
  • Treatment-naïve, non-cirrhotic patients
  • Early-stage disease
  • Patients at high risk for steroid side effects 1
• Important caveat: Do not use budesonide in cirrhotic patients or those with portosystemic shunts due to risk of side effects 1

Treatment Goals and Monitoring

Treatment Goals

• Complete normalization of transaminases and IgG levels 1
• Resolution of symptoms
• Histological improvement to normal or near normal 1

Monitoring

• Monitor serum AST/ALT and gamma-globulin levels regularly
• Consider liver biopsy to confirm histological remission before considering treatment withdrawal 1
• Monitor for bone disease with baseline and annual bone mineral densitometry in patients on long-term corticosteroid treatment 1
• Provide calcium and vitamin D supplementation to prevent osteoporosis 1

Treatment Duration

• Continue treatment for at least 2 years
• Maintain for at least 12 months after normalization of transaminases 1
• 80-90% of patients show improvement in transaminases after starting immunosuppressive treatment 1
• Only approximately 20% achieve sustained remission after withdrawal of immunosuppressive treatment 1

Common Pitfalls and Caveats

1. Failure to recognize non-response: If there's inadequate response, reconsider diagnosis or evaluate adherence to treatment 1
2. Undertreatment: Incomplete normalization of transaminases predicts relapse after treatment withdrawal, disease activity on liver biopsy, progression to cirrhosis, and poor outcome 1
3. Inadequate monitoring: Regular monitoring of liver enzymes is essential to guide therapy and detect early relapse
4. Premature discontinuation: Treatment withdrawal before complete biochemical and histological remission increases risk of relapse
5. Ignoring comorbidities: Assess for and manage steroid-related complications (diabetes, hypertension, osteoporosis)

The combination of prednisone and azathioprine represents the cornerstone of initial therapy for autoimmune hepatitis, with treatment decisions guided by disease severity, patient characteristics, and monitoring of response.