Management of Autoimmune Hepatitis in Flare or Liver Failure
For AIH flare without liver failure, immediately initiate high-dose prednisone 30 mg daily combined with azathioprine 50 mg daily (or 1-2 mg/kg/day), tapering prednisone to 10 mg daily over 4 weeks while maintaining azathioprine; for patients with liver failure or severe decompensation, start high-dose prednisone 60 mg daily (or 30 mg daily with azathioprine 150 mg daily) and simultaneously contact a liver transplant center. 1
Immediate Assessment and Risk Stratification
Determine severity within 2 weeks of presentation to guide management decisions. Look specifically for:
- Bilirubin levels and trajectory: Hyperbilirubinemia that fails to improve after 2 weeks of treatment predicts need for urgent transplantation 1, 2
- MELD score: If ≥15 or not rapidly improving on treatment, immediate transplant center contact is mandatory 1, 2
- Hepatic encephalopathy: Development or worsening despite treatment indicates transplant evaluation 2
- Multiacinar/bridging necrosis on biopsy: Predicts treatment failure and need for transplantation 1, 2
- Ascites: Most common sign of decompensation requiring transplant consideration 1, 2
Treatment Protocol for AIH Flare (Without Liver Failure)
Standard Flare Management
Initiate combination therapy immediately with prednisone 30 mg daily plus azathioprine 50 mg daily (or 1-2 mg/kg/day). 1, 3, 4 This combination produces significantly fewer corticosteroid-related side effects than high-dose prednisone alone (10% versus 44%). 1, 3, 4
Taper prednisone over 4 weeks to 10 mg daily while maintaining azathioprine at the same dose. 1, 3, 4 The tapering schedule is:
- Week 1: Prednisone 30 mg + Azathioprine 50 mg
- Week 2: Prednisone 20 mg + Azathioprine 50 mg
- Week 3: Prednisone 15 mg + Azathioprine 50 mg
- Week 4 onward: Prednisone 10 mg + Azathioprine 50 mg 1
Delay azathioprine initiation if bilirubin >6 mg/dL (100 μmol/L); start azathioprine ideally 2 weeks after steroid initiation once bilirubin improves. 1, 4
Monitoring Response
Assess treatment response at 2 weeks: Serum aminotransferases should improve within 2 weeks of starting therapy. 3, 4, 2 Favorable indicators include:
- Resolution of at least one laboratory abnormality
- Improvement in hyperbilirubinemia
- Failure of any test to worsen during treatment 1, 2
Monitor monthly thereafter: Small decrements in prednisone can cause marked increases in aminotransferases. 3 Continue treatment until complete normalization of transaminases AND IgG levels. 1, 3, 4
Treatment Protocol for Liver Failure or Severe Decompensation
High-Dose Corticosteroid Therapy
All decompensated patients warrant a corticosteroid trial before proceeding to transplantation, even those with advanced disease, ascites, or low-grade encephalopathy. 1, 2 Some will improve sufficiently to avoid immediate transplantation. 1, 2
Two high-dose regimens are endorsed by AASLD guidelines: 1, 2
- Prednisone 60 mg daily alone, OR
- Prednisone 30 mg daily + azathioprine 150 mg daily
Maintain high-dose therapy for at least 1 month, then reduce by 10 mg prednisone and 50 mg azathioprine monthly as clinical and laboratory findings improve, until reaching conventional maintenance doses (prednisone 10-20 mg daily, azathioprine 50 mg daily). 1
Critical Pitfall: Early Transplant Referral
Contact transplant center immediately if any of the following are present: 1, 2
- Liver failure at presentation
- MELD score >15
- Bilirubin not improving after 2 weeks of treatment
- Development or worsening of hepatic encephalopathy
- Clinical decompensation (ascites, variceal bleeding, hepatorenal syndrome)
Do NOT delay referral waiting for treatment response in severely ill patients. The 2-week assessment window determines transplant urgency. 1, 2
Special Considerations for Children
Children with treatment failure (5-15% of cases) should receive the same high-dose regimens as adults and be considered for transplantation. 1, 2 However, recurrent AIH post-transplant is more frequent in children than adults and may be less responsive to treatment, resulting in graft loss. 1, 2
Alternative Agents for Refractory Cases
If standard high-dose therapy fails after 1 month, consider: 1
- Tacrolimus (starting 0.075 mg/kg daily): May be more effective for refractory disease 4
- Cyclosporine (2-5 mg/kg daily): Effective in some treatment failures 1, 4
- Mycophenolate mofetil (1-2 g daily): First-line for azathioprine intolerance, but limited efficacy in true treatment failure 1, 4
Ursodeoxycholic acid and budesonide have been evaluated and shown negative results as salvage therapies. 1
Long-Term Management After Flare Resolution
Continue treatment for at least 2 years and for at least 12 months after complete normalization of transaminases and IgG. 1, 3, 4 Relapse occurs in 50-90% within 12 months of stopping treatment. 1, 3
After relapse, indefinite maintenance therapy is advisable: Use azathioprine 2 mg/kg daily alone or low-dose prednisone combinations, with 87% remaining in remission during median 67-month follow-up. 3, 5
Transplant Outcomes
Liver transplantation is highly successful in AIH with 5-year survival of 75-92% and 10-year survival of 75%. 1, 2 Recurrent AIH occurs in approximately 30% of adults post-transplant but is typically mild and manageable with prednisone and calcineurin inhibitor combinations. 1, 2