*Purpose: To investigate trends in induction therapy use in pediatric liver transplantation (LT) in the U.S. and evaluate the potential benefits and risks of induction immunosuppression in this population.

*Methods: This is a retrospective cohort study of 2,748 pediatric (<18 years) first LT alone recipients at 24 centers between 2006-2017 using data from the Pediatric Health Information System (PHIS) linked to the United Network for Organ Sharing database. Induction therapy was captured using day-by-day inpatient pharmacy billing data from PHIS. Clinical outcomes were ascertained using International Classification of Diseases diagnosis codes in PHIS. The association of induction therapy (none or steroid only vs IL2 receptor antagonist (IL2Ra) vs anti-thymocyte globulin (ATG) vs other or combination) with graft and patient survival was evaluated with multivariable time-to-event analysis. Mixed-effects logistic regression was used to study its association with acute rejection (AR) and opportunistic infections (OI) in the first year and post-transplant lymphoproliferative disease (PTLD) in the first two years post-LT.

*Results: Overall, 58.6% received none/steroid-only, 28.1% IL2Ra, 10.9% ATG and 2.5% other/combination induction. Children receiving ATG were more often older (p<0.001) and on dialysis at LT (p<0.001). Induction practices correlated with pediatric LT experience: e.g., 57.4% of recipients at low (<7 LTs/year) volume centers received IL2Ra compared to 23.2% at intermediate (7-14 LTs/year) and 24.3% at high (15+ LTs/year) volume centers (p<0.001 overall). There was little change in practice over time: e.g., 27.0% received IL2Ra in 2005 versus 32.0% in 2017, while 13.8% received ATG in 2005 versus 11.2% in 2017 (p=0.012). In multivariable analyses, observed benefits of induction therapy included improved patient and graft survival with ATG vs none/steroid-only induction among non-tumor recipients (n=2,455) with adjusted HRs of 0.56 (p=0.043) and 0.56 (p=0.002), respectively, and reduced AR during year 1 with IL2Ra with adjusted OR 0.65 (p=0.002). Potential risks included increased readmission for OI during year 1 with ATG (adjusted OR 1.62 vs none/steroid-only, p=0.029), and increased PTLD with IL2Ra (adjusted OR 1.97 vs none/steroid-only; p=0.020).

*Conclusions: In a large pediatric LT cohort, ATG was associated with a more favorable risk-benefit profile than none/steroid-only induction or IL2Ra therapy.

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