Treatment of Autoimmune Hepatitis
The standard first-line treatment for autoimmune hepatitis is combination therapy with prednisone 30 mg/day (tapering to 10 mg/day over 4 weeks) plus azathioprine 1-2 mg/kg/day, continued for at least 2 years and for at least 12 months after complete normalization of liver enzymes and IgG levels. 1, 2, 3
Initial Treatment Regimen
Combination therapy is superior to monotherapy, producing significantly fewer corticosteroid-related side effects (10% versus 44%) while achieving remission in 80-90% of patients. 1, 3
Standard Dosing Schedule:
- Week 1: Prednisone 30 mg/day + Azathioprine 50 mg/day (US) or 1-2 mg/kg/day (Europe) 1, 2
- Week 2: Prednisone 20 mg/day + Azathioprine (same dose) 2
- Weeks 3-4: Prednisone 15 mg/day + Azathioprine (same dose) 2
- Maintenance: Prednisone 10 mg/day + Azathioprine (same dose) until treatment endpoint 1, 2
Important Timing Consideration:
The European Association for the Study of the Liver recommends starting prednisone first, then adding azathioprine after 2 weeks, particularly when bilirubin is below 6 mg/dL—this is safer in patients with severe hyperbilirubinemia. 2, 3
Alternative First-Line Options
Prednisone Monotherapy:
Use prednisone alone (starting at 60 mg daily, tapering to 20 mg maintenance) in specific situations: 3
- Pre-existing cytopenia
- Pregnancy
- Thiopurine methyltransferase (TPMT) deficiency
- Active malignancy
Check TPMT activity before starting azathioprine to exclude homozygote deficiency, especially in patients with pre-existing leucopenia. 2, 3
Budesonide-Based Therapy:
Budesonide 9 mg/day plus azathioprine may be used only in treatment-naive, non-cirrhotic patients with early-stage disease who face high risk of steroid side effects. 2, 3
Critical caveat: Budesonide should NOT be used in patients with cirrhosis or acute severe autoimmune hepatitis due to risk of systemic side effects and inadequate efficacy. 3
Treatment Goals and Monitoring
Complete normalization of BOTH serum aminotransferases AND IgG levels must be the treatment goal—persistent elevations predict relapse, ongoing histological activity, progression to cirrhosis, and poor outcomes. 2
Monitoring Schedule:
- Initial response assessment: 4-8 weeks after treatment initiation 1, 2
- Early improvement: Serum aminotransferase levels should improve within 2 weeks of starting therapy 1, 3
- Monthly monitoring: Check serum aminotransferase levels monthly, as small decrements in prednisone dose can trigger marked increases 1
- Time to normalization: Average duration is 19 months, with 66-91% achieving normal liver tests within 2 years 2
Biochemical remission achieved within 6 months is associated with lower frequency of progression to cirrhosis. 1
Pre-Treatment Withdrawal Assessment:
Liver biopsy assessment prior to termination of treatment is recommended to ensure full resolution—55% of patients with normal serum enzymes still show persistent interface hepatitis on biopsy. 3
Management of Acute Severe Autoimmune Hepatitis
For acute severe presentations, immediately administer high-dose intravenous corticosteroids (≥1 mg/kg) as early as possible. 2, 3
If no improvement occurs within 7 days, list for emergency liver transplantation. 2, 3
Treatment Failure and Second-Line Options
Definition and Initial Management:
For confirmed non-responders, increase to high-dose therapy: 2, 3
- Prednisone 60 mg daily alone, OR
- Prednisone 30 mg daily plus azathioprine 150 mg daily
- Continue for at least 1 month
Second-Line Agents for Steroid-Refractory Cases:
Mycophenolate mofetil (MMF) is recommended as the first second-line agent, particularly for azathioprine intolerance: 3
- Initial dose: 1 g daily
- Maintenance: 1.5-2 g daily
Tacrolimus may be more effective for refractory disease not responding to standard therapy: 1, 3
- Starting dose: 0.075 mg/kg daily
Cyclosporine has shown effectiveness in inducing and maintaining remission: 1, 3
- Dose: 2-5 mg/kg daily
- Particularly effective in pediatric patients 3
Long-Term Management and Relapse
Relapse occurs in 50-90% of patients within 12 months of stopping treatment, even after achieving complete biochemical and histological remission. 1, 2
Only 20-28% achieve sustained remission off therapy. 2
After Relapse:
- Re-treat with combination prednisone and azathioprine therapy 1
- Consider long-term maintenance with azathioprine 2 mg/kg/day 1, 2
- For patients who have relapsed more than once, 87% remain in remission during long-term maintenance (median 67 months) 1
Prevention of Treatment Complications
All patients should receive: 1, 2
- Calcium and vitamin D supplementation
- DEXA scanning at 1-2 year intervals to monitor bone mineral density
- Early vaccination against hepatitis A and B in susceptible patients
Timeline of Complications:
Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of therapy at prednisone doses >10 mg daily. 1, 3
Cosmetic side effects occur in 80% of patients after 2 years of treatment. 3
Minimize cumulative steroid exposure to reduce the risk of these complications. 2