Thalji Leanne, Thalji Nassir M, Heimbach Julie K, Ibrahim Samar H, Kamath Patrick S, Hanson Andrew, Schulte Phillip J, Haile Dawit T, Kor Daryl J
Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMN.
Department of SurgeryMayo ClinicRochesterMN.
Hepatology. 2021 Mar;73(3):1117-1131. doi: 10.1002/hep.31397.
Reliance on exception points to prioritize children for liver transplantation (LT) stems from concerns that the Pediatric End-Stage Liver Disease (PELD) score underestimates mortality. Renal dysfunction and serum sodium disturbances are negative prognosticators in adult LT candidates and various pediatric populations, but are not accounted for in PELD. We retrospectively evaluated the effect of these parameters in predicting 90-day wait-list death/deterioration among pediatric patients (<12 years) listed for isolated LT in the United States between February 2002 and June 2018.
Among 4,765 patients, 2,303 (49.3%) were transplanted, and 231 (4.8%) died or deteriorated beyond transplantability within 90 days of listing. Estimated glomerular filtration rate (eGFR) (hazard ratio [HR] 1.09 per 5-unit decrease, 95% confidence interval [CI] 1.06-1.10) and dialysis (HR 7.24, 95% CI 3.57-14.66) were univariate predictors of 90-day death/deterioration (P < 0.001). The long-term benefit of LT persisted in patients with renal dysfunction, with LT as a time-dependent covariate conferring a 2.4-fold and 17-fold improvement in late survival among those with mild and moderate-to-severe dysfunction, respectively. Adjusting for PELD, sodium was a significant nonlinear predictor of outcome, with 90-day death/deterioration risk increased at both extremes of sodium (HR 1.20 per 1-unit decrease below 137 mmol/L, 95% CI 1.16-1.23; HR per 1-unit increase above 137 mmol/L 1.13, 95% CI 1.10-1.17, P < 0.001). A multivariable model incorporating PELD, eGFR, dialysis, and sodium demonstrated improved performance and superior calibration in predicting wait-list outcomes relative to the PELD score.
Listing eGFR, dialysis, and serum sodium are potent, independent predictors of 90-day death/deterioration in pediatric LT candidates, capturing risk not accounted for by PELD. Incorporation of these variables into organ allocation systems may highlight patient subsets with previously underappreciated risk, augment ability of PELD to prioritize patients for transplantation, and ultimately mitigate reliance on nonstandard exceptions.
基于例外情况来优先安排儿童进行肝移植(LT),这源于人们担心儿童终末期肝病(PELD)评分会低估死亡率。肾功能不全和血清钠紊乱在成人肝移植候选者及各类儿科人群中是不良预后指标,但在PELD评分中未予以考虑。我们回顾性评估了这些参数对2002年2月至2018年6月期间在美国登记等待单纯肝移植的12岁以下儿科患者90天等待名单上死亡/病情恶化情况的预测作用。
在4765例患者中,2303例(49.3%)接受了移植,231例(4.8%)在登记后90天内死亡或病情恶化至无法进行移植。估计肾小球滤过率(eGFR)(每降低5个单位的风险比[HR]为1.09,95%置信区间[CI]为1.06 - 1.10)和透析(HR为7.24,95% CI为3.57 - 14.66)是90天死亡/病情恶化的单因素预测指标(P < 0.001)。肝移植对肾功能不全患者的长期益处依然存在,将肝移植作为时间依赖性协变量时,轻度和中度至重度肾功能不全患者的晚期生存率分别提高了2.4倍和17倍。在对PELD进行校正后,钠是结局的显著非线性预测指标,在钠水平的两个极端情况下,90天死亡/病情恶化风险均增加(低于137 mmol/L时,每降低1个单位的HR为1.20,95% CI为1.16 - 1.23;高于137 mmol/L时,每升高1个单位的HR为1.13,95% CI为1.10 - 1.17,P < 0.001)。一个纳入了PELD、eGFR、透析和钠的多变量模型在预测等待名单结局方面相对于PELD评分表现出更好的性能和更高的校准度。
登记时的eGFR、透析和血清钠是儿科肝移植候选者90天死亡/病情恶化的有力独立预测指标,可捕捉PELD未考虑到的风险。将这些变量纳入器官分配系统可能会凸显出之前未被充分认识到风险的患者亚组,增强PELD对患者进行移植优先排序的能力,并最终减少对非标准例外情况的依赖。