Benefits and risks of induction immunosuppression in pediatric autoimmune liver disease from SPLIT Registry

The optimal induction regimen for pediatric liver transplantation (LT) in patients with Autoimmune Liver Disease (AILD) is not well-defined. This study compared outcomes between corticosteroids only, anti-thymocyte globulin (ATG), and IL-2 receptor antagonists (IL2RA; Basiliximab/Daclizumab). A retrospective review of 445 pediatric LT recipients with AILD (Autoimmune hepatitis, primary sclerosing cholangitis, or autoimmune sclerosing cholangitis) was conducted using the SPLIT database. Re-transplants were excluded. Primary outcomes included biopsy-confirmed rejection, culture-proven infection, graft loss, and mortality. Baseline demographics were comparable across groups. At 30 days post-LT, the IL2RA group demonstrated a significantly lower rate of biopsy-confirmed rejection (11.2%) compared to corticosteroids only (20.9%) and ATG (28%; p=0.05). Conversely, the ATG group experienced a significantly higher incidence of culture-proven infections between days 30-90 (42.9%) compared to corticosteroids only (10.2%) and IL2RA (17.9%; p=0.03). In multivariable-adjusted models, ATG induction was associated with a 10-fold higher risk of sub-acute culture-proven infection at 30-90 days (aOR=10.0, 95%CI: 1.4-71.8, p=0.02) compared to corticosteroids alone. However, neither ATG (aOR=0.47) nor IL-2RA (aOR=0.63) significantly altered the odds of early acute rejection at 0-30 days (p>0.30). No significant differences were observed in graft loss, mortality, disease recurrence, or post-transplant lymphoproliferative disorder up to five years post-transplant. In pediatric AILD, induction with IL2RA significantly reduces early acute rejection without increasing infection risks or compromising long-term graft and patient survival.