What is the typical treatment for autoimmune hepatitis?

Treatment of Autoimmune Hepatitis

The standard first-line treatment for autoimmune hepatitis is combination therapy with prednisolone 30 mg/day (tapering to 10 mg/day over 4 weeks) plus azathioprine 1-2 mg/kg/day, which achieves remission in 80-90% of patients and dramatically reduces corticosteroid-related side effects compared to steroid monotherapy. 1

First-Line Treatment Regimen

Standard Combination Therapy

• Start prednisolone at 30 mg/day and taper to 10 mg/day over the first 4 weeks 1
• Add azathioprine at 50 mg/day initially (when bilirubin is below 6 mg/dL), ideally beginning two weeks after starting steroids, then increase to maintenance dose of 1-2 mg/kg/day 1, 2
• This combination produces significantly fewer corticosteroid-related side effects (10% versus 44%) compared to prednisone monotherapy 1, 3

Alternative First-Line Options

• Prednisone monotherapy (60 mg daily, tapering to 40 mg, 30 mg, then maintenance at 20 mg) is appropriate for patients with cytopenia, pregnancy, thiopurine methyltransferase deficiency, or malignancy 1
• Budesonide 9 mg/day with azathioprine may be considered as an alternative, but should NOT be used in patients with cirrhosis or acute severe AIH due to risk of systemic side effects from impaired first-pass metabolism 1, 2

Treatment Goals and Monitoring

Target Endpoints

• Aim for complete normalization of liver enzymes (AST, ALT) and IgG levels—this reduces the relative risk of relapse after drug withdrawal by 3-fold to 11-fold 1, 2
• Serum aminotransferase levels should improve within 2 weeks of starting therapy 1, 3
• Most patients achieve biochemical remission within 6-12 months 2, 3

Duration and Assessment

• Continue treatment for at least 2 years before considering withdrawal 1, 2
• Perform liver biopsy assessment prior to termination of treatment to ensure full resolution—55% of patients with normal serum enzymes still have persistent interface hepatitis on histology 1
• Failure to achieve complete normalization of liver enzymes and IgG levels leads to almost universal relapse after treatment withdrawal 1, 2

Management of Treatment Failure or Intolerance

Second-Line Agents

• Mycophenolate mofetil (MMF) is the first choice for azathioprine intolerance: start at 1 g daily, increase to maintenance of 1.5-2 g daily 1, 2
• Tacrolimus (starting dose 0.075 mg/kg daily) is more effective for refractory disease not responding to standard therapy 1, 2
• Cyclosporine (2-5 mg/kg daily) has shown effectiveness in inducing and maintaining remission, particularly in pediatric patients 1, 4

Incomplete Response Strategy

• For incomplete response, use long-term low-dose corticosteroid therapy with gradual decrease to 10 mg daily 1
• Long-term azathioprine (2 mg/kg daily) can stabilize liver enzymes in corticosteroid-intolerant individuals 1, 3

Special Clinical Scenarios

Acute Severe Autoimmune Hepatitis

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

Pediatric Patients

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

Relapse Management

• Relapse occurs in 50-90% of patients within 12 months of stopping treatment 3
• After relapse, consider long-term maintenance with azathioprine 2 mg/kg/day 3
• For patients who have relapsed more than once, 87% remain in remission on long-term combination therapy or azathioprine monotherapy 3

Critical Pitfalls and Monitoring

Pre-Treatment Considerations

• Measure thiopurine methyltransferase (TPMT) before azathioprine initiation to exclude homozygote deficiency, especially in patients with pre-existing leucopenia 1, 2
• Vaccinate against hepatitis A and B early in susceptible patients 3

Corticosteroid Complications

• Cosmetic side effects occur in 80% of patients after 2 years of treatment 1
• Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months at prednisone doses >10 mg daily 1, 2
• All patients should receive calcium and vitamin D supplementation 3
• Monitor bone mineral density with DEXA scanning at 1-2 year intervals 3

Azathioprine Toxicity

• Azathioprine hepatotoxicity is more common in patients with advanced liver disease—monitor closely 2
• Small decrements in prednisone dose can be associated with marked increases in aminotransferase levels—monitor monthly 3