What is the typical treatment for autoimmune hepatitis?

Treatment of Autoimmune Hepatitis

The standard first-line treatment for autoimmune hepatitis is prednisolone 30 mg/day (tapered to 10 mg/day over 4 weeks) plus azathioprine 1-2 mg/kg/day (typically 50 mg/day), which achieves remission in 80-90% of patients and significantly improves survival. 1

First-Line Treatment Regimen

Combination therapy is superior to monotherapy because it reduces corticosteroid-related side effects from 44% to only 10% compared to prednisone alone. 1

Standard Dosing Protocol:

• Prednisolone: Start at 30 mg/day, then taper to 10 mg/day over 4 weeks 1
• Azathioprine: 1-2 mg/kg/day (typically 50 mg/day initially, increasing to maintenance of 1-2 mg/kg based on response) 2
• Critical timing: Initiate azathioprine only when bilirubin is below 6 mg/dL, ideally two weeks after starting steroids 1, 2

Alternative First-Line Option:

Prednisone monotherapy is appropriate for specific contraindications: cytopenia, pregnancy, thiopurine methyltransferase (TPMT) deficiency, or malignancy. 1 Start at 60 mg daily, then taper to 40 mg, 30 mg, and maintain at 20 mg until endpoint. 3

Budesonide Consideration:

Budesonide 9 mg/day with azathioprine may be used as first-line therapy, but is absolutely contraindicated in cirrhotic patients or acute severe AIH due to risk of systemic side effects from impaired first-pass metabolism. 1, 2

Treatment Goals and Monitoring

The goal is complete normalization of liver enzymes (AST, ALT) AND IgG levels—not just improvement. 1, 2 This distinction is critical because:

• Normalization of laboratory indices before treatment termination reduces relapse risk by 3-fold to 11-fold 1
• Persistent enzyme elevations predict relapse, ongoing histologic activity, progression to cirrhosis, and poor outcomes 2

Monitoring Timeline:

• Within 2 weeks: Serum aminotransferases should begin improving 1, 3
• Within 6 months: Biochemical remission at this point predicts lower progression to cirrhosis 3
• Before stopping treatment: Liver biopsy is recommended to ensure full histologic resolution, as 55% of patients with normal enzymes still have persistent interface hepatitis 1

Treat for at least 2 years before considering withdrawal, as failure to achieve complete normalization leads to almost universal relapse. 1

Management of Acute Severe AIH

Administer high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 1, 2, 3 If no improvement within 7 days, immediately evaluate for liver transplantation. 1, 3

Second-Line Therapy for Treatment Failure or Intolerance

When to Consider Second-Line:

• Incomplete response despite adequate first-line therapy
• Azathioprine intolerance or toxicity
• Confirmed diagnosis with documented adherence but suboptimal response 2

Recommended Second-Line Agents (in order):

1. Mycophenolate Mofetil (MMF) - First choice for second-line therapy, especially for azathioprine intolerance:

• Initial dose: 1 g daily
• Maintenance: 1.5-2 g daily 1

2. Tacrolimus - More effective for refractory disease not responding to standard therapy:

• Starting dose: 0.075 mg/kg daily 1

3. Cyclosporine - Effective for inducing and maintaining remission, particularly in pediatric patients:

• Dose: 2-5 mg/kg daily 1
• In pediatric studies, 94% achieved normal aminotransferases, with 72% within 6 months 4

For Incomplete Response:

Consider long-term low-dose corticosteroid therapy (gradual decrease to 10 mg daily), and long-term azathioprine (2 mg/kg daily) can stabilize liver enzymes in corticosteroid-intolerant individuals. 1

Special Populations

Pediatric Patients:

Treatment regimens mirror adults with dose adjustments, but early use of azathioprine (1-2 mg/kg daily) or 6-mercaptopurine (1.5 mg/kg daily) is recommended to minimize steroid effects on growth. 1 Response is excellent, with normalization of liver tests in 75-90% after 6-9 months. 1

AIH-PBC Overlap Syndrome:

Combined therapy with ursodeoxycholic acid (UDCA) and immunosuppressants is recommended. 2

Critical Pitfalls and Caveats

Before Starting Azathioprine:

Measure TPMT levels to exclude homozygote deficiency, especially in patients with pre-existing leucopenia. 1, 2 Azathioprine hepatotoxicity is more common in advanced liver disease. 2

Corticosteroid Side Effects:

• Cosmetic effects: Occur in 80% of patients after 2 years (facial rounding, acne, dorsal hump, truncal obesity) 3
• Severe complications: Develop after 18 months at prednisone doses >10 mg daily (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) 1, 3
• Bone monitoring: Baseline and annual bone mineral densitometry for patients on long-term corticosteroids 3

Treatment Withdrawal:

Never withdraw therapy in patients who have not achieved complete normalization of biochemistry with normal histology, nonspecific portal hepatitis, or inactive cirrhosis. 1 Liver biopsy may show persistent interface hepatitis in 55% of patients with normal serum enzymes. 1

Non-Response Management:

Failure of adequate response should prompt reconsideration of diagnosis or evaluation of treatment adherence before escalating therapy. 2, 3