What is the initial treatment for a patient with abnormal liver function tests indicating autoimmune hepatitis?

Initial Treatment for Autoimmune Hepatitis

The first-line treatment for autoimmune hepatitis is prednisolone (or prednisone) plus azathioprine, which achieves remission in 80-90% of patients and significantly improves survival compared to no treatment. 1

Standard Treatment Regimen

Initial Therapy

• Start with prednisolone 30 mg/day (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day 2, 1
• Higher initial doses of prednisolone (up to 1 mg/kg/day or 60 mg/day) may result in more rapid normalization of liver enzymes in severe cases 2
• The combination regimen of prednisone and azathioprine is associated with a lower occurrence of corticosteroid-related side effects than higher dose prednisone regimen alone (10% versus 44%) 2
• Azathioprine should be initiated when bilirubin levels are below 6 mg/dl, ideally two weeks after starting steroid treatment 1

Dosing Schedule

• Week 1: Prednisolone 30 mg/day, azathioprine 1 mg/kg/day 2
• Week 2: Prednisolone 20 mg/day, azathioprine 1 mg/kg/day 2
• Week 3-4: Prednisolone 15 mg/day, azathioprine 1 mg/kg/day 2
• Maintenance: Prednisolone 10 mg/day or less, azathioprine 1-2 mg/kg/day 2

Pre-Treatment Evaluation

• TPMT (thiopurine methyltransferase) measurement should be considered before starting azathioprine to exclude homozygote TPMT deficiency, especially in patients with pre-existing leucopenia 2, 1
• Baseline bone mineral densitometry is recommended for patients who will be on long-term corticosteroid treatment 2
• Assess for contraindications to standard therapy, including severe cytopenia, pregnancy, or malignancy 2

Treatment Goals and Monitoring

• The primary treatment goal is complete normalization of liver enzymes and IgG levels 2, 1
• Persistent elevations of liver enzymes predict relapse after treatment withdrawal, ongoing inflammation on liver biopsy, progression to cirrhosis, and poor outcomes 1
• Monitor liver function tests regularly during treatment adjustment phase 2
• Daily maintenance doses should remain fixed until treatment goals are achieved, as dose titrations are associated with delayed or incomplete histological improvement 2

Special Populations

Children and Adolescents

• Initial treatment with prednisone 1-2 mg/kg daily (up to 60 mg/day) for two weeks, either alone or with azathioprine 1-2 mg/kg daily 2
• Taper prednisone over 6-8 weeks to 0.1-0.2 mg/kg daily or 5 mg daily 2
• Early use of azathioprine is recommended for all children without contraindications to minimize corticosteroid effects on growth 2

Elderly Patients

• Caution is advised with high-dose prednisolone in frail elderly patients 2
• The combination regimen is particularly preferred in elderly patients due to lower steroid-related complications 3

Alternative First-Line Options

• Budesonide (9 mg daily) in combination with azathioprine may be considered for non-cirrhotic patients who are at high risk for corticosteroid side effects 2, 1
• Budesonide should not be used in cirrhotic patients due to risk of systemic side effects 1

Management of Suboptimal Response

• If there is inadequate response to standard therapy, consider:
  • Increasing prednisolone to 60 mg/day (for at least one month) and azathioprine to 2 mg/kg/day 2
  • Evaluating for non-compliance or altered metabolism of azathioprine 2
  • Consulting with a liver specialist for consideration of second-line agents such as mycophenolate mofetil or tacrolimus 2, 1

Common Pitfalls and Considerations

• Azathioprine hepatotoxicity is more common in patients with advanced liver disease 1
• Patients on long-term corticosteroid treatment should be monitored for bone disease 2
• Liver biopsy assessment prior to termination of treatment is the only method to ensure full resolution of the disease 2
• The average duration of treatment is 18-24 months before considering withdrawal 2