What is the initial treatment for autoimmune hepatitis?

Initial Treatment for Autoimmune Hepatitis

The first-line treatment for autoimmune hepatitis is a combination of prednisolone (or prednisone) and azathioprine, with prednisolone typically started at 0.5-1 mg/kg/day (30-60 mg/day) and azathioprine at 50 mg/day initially, increasing to 1-2 mg/kg/day as maintenance. 1

Standard Treatment Regimen

Initial Combination Therapy

• Start with prednisolone 30-60 mg/day
• Add azathioprine 50 mg/day after 2 weeks, then increase to maintenance dose of 1-2 mg/kg/day (typically 100 mg/day for a 60kg patient)
• Follow a tapering schedule for prednisolone:
  • Week 1: 60 mg/day
  • Week 2: 50 mg/day
  • Week 3: 40 mg/day (add azathioprine 50 mg/day)
  • Week 4: 30 mg/day
  • Week 5: 25 mg/day (increase azathioprine to 100 mg/day)
  • Week 6: 20 mg/day
  • Weeks 7-8: 15 mg/day
  • Weeks 9-10: 12.5 mg/day
  • Beyond 10 weeks: 10 mg/day 1

Alternative First-Line Option

For non-cirrhotic patients without severe acute hepatitis or liver failure:

• Budesonide (9 mg/day) in combination with azathioprine
• Advantages: fewer steroid-related side effects
• Contraindicated in cirrhotic patients or those with portosystemic shunts 1

Special Situations

Prednisolone Monotherapy (60 mg/day initially)

Appropriate for:

• Patients with cytopenia who cannot tolerate azathioprine
• Pregnant patients
• Patients with thiopurine methyltransferase (TPMT) deficiency 1

TPMT Testing

• Test for TPMT activity prior to azathioprine initiation to identify patients at risk for severe myelosuppression
• Patients with near-zero erythrocyte concentrations of TPMT are at risk for myelosuppression during azathioprine treatment
• Patients with decreased but not extreme reductions in TPMT activity can tolerate azathioprine at lower doses (50 mg) 2, 1

Monitoring and Treatment Duration

Monitoring Schedule

• Weekly liver tests and blood counts for the first 4 weeks
• Monthly monitoring once stable
• Clinical improvement should be evident within 2 weeks
• 80-90% of patients achieve laboratory remission within 6-12 months 1

Treatment Endpoints

1. Remission: Disappearance of symptoms, normal serum aminotransferases, bilirubin and γ-globulin levels, normal hepatic tissue or inactive cirrhosis
2. Treatment Failure: Worsening clinical, laboratory, and histological features despite compliance with therapy
3. Incomplete Response: Some or no improvement in clinical, laboratory, and histological features after 2-3 years of therapy
4. Drug Toxicity: Development of intolerable side effects 2

Duration

• Minimum treatment duration is 24 months
• Consider liver biopsy after 2 years to confirm histological remission
• After remission, gradually withdraw prednisolone over a 6-week period
• Monitor serum AST/ALT, bilirubin, and γ-globulin levels at 3-week intervals during and for 3 months after drug withdrawal 2, 1

Second-Line Therapy

For patients who fail first-line therapy:

• Mycophenolate mofetil (MMF): preferred for azathioprine intolerance
• Tacrolimus: more effective than MMF for non-responders (56% vs 34% remission rate)
• Cyclosporine: may be considered as salvage therapy 1

Important Considerations

Pregnancy

• Azathioprine has a category D pregnancy rating by the FDA
• Should be discontinued if possible during pregnancy
• Resume standard therapy 2 weeks prior to anticipated delivery
• Monitor serum AST/ALT levels at 3-week intervals for at least 3 months after delivery 2

Side Effect Management

• Provide calcium and vitamin D supplementation to all patients on steroids
• Consider DEXA scanning at 1-2 year intervals
• For corticosteroid-related complications (osteopenia, emotional instability, hypertension, diabetes), consider reducing dose or switching to alternative regimen 2, 1

Treatment Efficacy

Research suggests that combination therapy with prednisone and azathioprine from the beginning of treatment achieves better efficacy in the induction phase compared to prednisone alone or delayed introduction of azathioprine 3. However, a recent European study found that initial prednisone doses below 0.50 mg/kg/day may be as effective as higher doses while reducing unnecessary steroid exposure 4.