Raghu Vikram K, Rothenberger Scott D, Squires James E, Eisenberg Elizabeth, Peters Anna L, Halma Jennifer, Antala Swati, Batsis Irini D, Zhang Ke-You, Feldman Amy G, Leung Daniel H, Lobritto Steven J, Bucuvalas John, Horslen Simon P, Mazariegos George V, Perito Emily R
Department of Pediatrics, University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pediatr Transplant. 2025 Feb;29(1):e70018. doi: 10.1111/petr.70018.
Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.
We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, and acute rejection rate within the first year after transplant.
The study cohort included 2542 LT recipients from 67 LT centers. Sixteen centers (24%) had no MMF variability; twenty-five centers (37%) had no induction variability. In multivariable analysis, induction CIV was associated with 2.72 times greater odds of acute rejection in the first year (OR 2.72; 95% CI 1.66-4.45; p < 0.001). MMF CIV was not associated with rejection (OR 1.22, 95% CI 0.66-2.25, p = 0.527). Neither one-year graft nor patient survival were associated with induction or MMF CIV.
Induction CIV is associated with higher one-year acute rejection odds and did not impact short-term graft or patient survival. Improved understanding of the reasons for high CIV will inform future work aiming to determine whether reducing variability may improve outcomes.
尽管存在机构协议，但肝移植中心在早期免疫抑制实践中往往存在差异。我们旨在衡量小儿肝移植（LT）后中心内早期免疫抑制的变异性，并研究其与一年期结局的关联。
我们分析了器官共享联合网络登记处2013年至2018年的小儿肝移植病例，数据按中心汇总。我们将诱导方案分为仅用皮质类固醇、T细胞耗竭抗体和非T细胞耗竭抗体。主要暴露因素为（1）诱导期和（2）霉酚酸酯（MMF）使用的免疫抑制变异性系数（CIV）。主要结局为移植后第一年内的一年期移植物存活率、患者存活率和急性排斥反应率。
研究队列包括来自67个肝移植中心的2542例肝移植受者。16个中心（24%）的MMF无变异性；25个中心（37%）的诱导无变异性。在多变量分析中，诱导期CIV与第一年急性排斥反应的几率高2.72倍相关（OR 2.72；95%CI 1.66 - 4.45；p < 0.001）。MMF CIV与排斥反应无关（OR 1.22，95%CI 0.66 - 2.25，p = 0.527）。一年期移植物存活率和患者存活率均与诱导期或MMF CIV无关。
诱导期CIV与较高的一年期急性排斥反应几率相关，且不影响短期移植物或患者存活率。更好地理解高CIV的原因将为未来旨在确定降低变异性是否可改善结局的工作提供信息。
