Initial Treatment for Autoimmune Hepatitis in Pediatric Patients
All children with confirmed autoimmune hepatitis should be treated immediately with combination therapy of prednisone (1-2 mg/kg/day, maximum 60 mg/day) plus azathioprine (1-2 mg/kg/day), as this regimen achieves excellent response rates of 75-90% normalization within 6-9 months while minimizing the growth-impairing effects of prolonged high-dose corticosteroids. 1
Why Treat All Pediatric Patients
Unlike adults where treatment indications are more selective, all children with established AIH diagnosis require immediate treatment because: 1
- More than 50% present with cirrhosis already established 1
- Disease appears more aggressive at presentation than in adults 1
- Delays in treatment adversely affect long-term outcomes 1
- The only exception is advanced cirrhosis without inflammatory activity 1
Standard Initial Regimen
Induction Phase (First 2 Weeks)
Start with high-dose prednisone 1-2 mg/kg/day (maximum 60 mg/day) combined with azathioprine 1-2 mg/kg/day. 1 The 2002 guidelines used 2 mg/kg/day prednisone 1, but the 2010 update refined this to 1-2 mg/kg/day 1, reflecting clinical experience that lower doses are often sufficient.
Tapering Schedule (Weeks 2-8)
Taper prednisone over 6-8 weeks to reach maintenance dose of 0.1-0.2 mg/kg/day or 5 mg/day, whichever is higher. 1 Keep azathioprine at the same dose throughout. 1
Why Combination Therapy is Critical in Children
Early addition of azathioprine is essential in pediatric AIH to minimize corticosteroid effects on linear growth, bone development, and physical appearance. 1 The combination regimen reduces corticosteroid-related side effects from 44% to 10% compared to prednisone monotherapy. 1
Monitoring Response
Almost all children show improvement in liver enzymes within 2-4 weeks of starting treatment. 1 Expect:
- 80-90% achieve laboratory remission in 6-12 months 1
- Monitor AST, ALT, bilirubin, and IgG levels at 4-6 week intervals 1
- Treat disease flares (rising transaminases) with temporary increase in corticosteroid dose 1
Alternative Regimen: Prednisone Monotherapy
Use prednisone alone (2 mg/kg/day, maximum 60 mg/day) only in specific circumstances: 1
- Severe pre-treatment cytopenia (WBC <2.5 × 10⁹/L or platelets <50 × 10⁹/L) 1
- Known thiopurine methyltransferase (TPMT) deficiency 1
- Active malignancy 1
- Pregnancy or contemplating pregnancy 1
However, this approach carries significantly higher risk of corticosteroid side effects and should be avoided when possible in children. 1
Special Consideration: Cyclosporine
Cyclosporine as initial treatment does not offer significant advantage over standard prednisone-azathioprine therapy and should be considered investigational. 1 A 2020 randomized trial showed similar effectiveness but remission was achieved earlier with prednisone-azathioprine (8.6 weeks) versus cyclosporine (13.6 weeks). 2 Reserve cyclosporine for refractory cases. 3
Treatment Goals and Duration
The goal is minimal or no serum transaminase abnormality on the lowest medication dose possible. 1 Specific targets:
- Continue treatment for at least 2-3 years 1
- Require normal liver tests and IgG for at least 1 year on low-dose therapy before considering withdrawal 1
- Perform liver biopsy before stopping treatment to confirm no histological inflammation 1
Critical Pitfall: High Relapse Rates
Relapse after drug withdrawal occurs in 60-80% of children, so parents must be counseled that retreatment is highly likely. 1 This is substantially higher than the 50-90% relapse rate seen in adults. 4
Managing Liver Failure at Presentation
If a child presents with liver failure (prothrombin time <50%):
Start standard immunosuppression immediately—90% of children recover liver function with a median time of 24 days. 5 Consider triple immunosuppression (adding cyclosporine) if liver failure persists after 1 week of standard therapy. 2 Infection is the most significant factor delaying recovery and causing mortality. 5
Maintenance Strategy
Long-term azathioprine monotherapy (1-2 mg/kg/day) is well-tolerated and effective for maintaining remission in children, allowing corticosteroid withdrawal. 1, 6 A 2022 study confirmed azathioprine monotherapy maintains remission effectively with relapse rates of only 17.9%. 6 Target 6-thioguanine levels of 50-250 pmol/8 × 10⁸ RBC are associated with biochemical remission—much lower than inflammatory bowel disease targets. 7