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低剂量类固醇确实有影响:儿童肝移植后线性生长受损的独立危险因素。

Low-dose steroids do make a difference: Independent risk factors for impaired linear growth after pediatric liver transplantation.

机构信息

Division of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.

Core Facility Quality Management & Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.

出版信息

Pediatr Transplant. 2021 Jun;25(4):e13989. doi: 10.1111/petr.13989. Epub 2021 Mar 10.

Abstract

Growth failure persists after pediatric liver transplantation and impairs pediatric development and quality of life. Steroid dose minimization attempts to prevent growth impairment, yet long-term assessment in pediatric liver recipients is lacking. We identified risk factors for impaired linear growth after pediatric liver transplantation, with a special focus on low-dose steroid therapy. This is a single-center retrospective analysis of height development in pediatric liver recipients up to 5 years after transplantation. Risk factors for impaired linear growth (height Z-scores≤-2) at transplantation, after two (n = 347) and five years (n = 210) were identified by univariate and multivariate logistic regression. At transplantation, growth retardation was found in 52.2%, predominantly younger children. Height Z-scores improved from -2.23 to -1.40 (SE 0.11; 95%CI 0.74-1.16; p < .001) two years and -1.19 (SE 0.07;0.08-0.34; p = .017) five years post-transplant. Multivariate analysis showed previous growth impairment (OR=1.484; 95%-CI=1.107-1.988; p = .004), graft loss (49.006;2.232-1076; p = .006), and prolonged cold ischemic time (1.034;1.007-1.061; p = .011) as main long-term risk factors; steroid use was a significant predictor of 2-year but not 5-year growth impairment. In univariate analysis, impaired growth after 2 and 5 years was associated with continuous low-dose (2.5 mg/m BSA) steroid therapy (OR=3.323;1.578-6.996; p < .001/OR=8.352;1.089-64.07; p = .006)and graft loss (OR=2.513;1.395-4.525; p = .003/OR=3.378;1.815-7.576; p < .001). Furthermore, indication and era of transplantation affected growth. Our results show significant catch-up growth after pediatric liver transplantation, yet growth failure strongly affects particularly young liver recipients. The main influenceable long-term risk factor is pre-existing growth failure, emphasizing the importance of early aggressive nutritional therapy. Moreover, low-dose steroid therapy might impair growth and should therefore be critically questioned in long-term immunosuppression.

摘要

儿童肝移植后生长发育不良持续存在,影响儿童生长发育和生活质量。尝试最小化类固醇剂量以预防生长发育不良,但缺乏对儿童肝移植受者的长期评估。我们确定了儿童肝移植后线性生长受损的危险因素,特别关注低剂量类固醇治疗。这是一项对儿童肝移植受者移植后 5 年内身高发育的单中心回顾性分析。通过单变量和多变量逻辑回归确定了移植时(n=347)和两年后(n=210)线性生长受损(身高 Z 评分≤-2)的危险因素。在移植时,生长迟缓见于 52.2%的患儿,主要是年龄较小的患儿。身高 Z 评分从移植后 2 年的-2.23 增加到-1.40(SE 0.11;95%CI 0.74-1.16;p<0.001),5 年时增加到-1.19(SE 0.07;0.08-0.34;p=0.017)。多变量分析显示,既往生长不良(OR=1.484;95%CI=1.107-1.988;p=0.004)、移植物丢失(49.006;2.232-1076;p=0.006)和冷缺血时间延长(1.034;1.007-1.061;p=0.011)是主要的长期危险因素;类固醇使用是 2 年生长不良的显著预测因素,但不是 5 年生长不良的预测因素。在单变量分析中,2 年和 5 年后的生长不良与持续低剂量(2.5mg/m2BSA)类固醇治疗(OR=3.323;1.578-6.996;p<0.001/OR=8.352;1.089-64.07;p=0.006)和移植物丢失(OR=2.513;1.395-4.525;p=0.003/OR=3.378;1.815-7.576;p<0.001)有关。此外,移植的适应证和时代也影响生长。我们的结果显示,儿童肝移植后存在显著的追赶生长,但生长发育不良严重影响特别是年轻的肝移植受者。主要的可影响的长期危险因素是预先存在的生长不良,这强调了早期积极营养治疗的重要性。此外,低剂量类固醇治疗可能会损害生长,因此在长期免疫抑制治疗中应受到严格质疑。

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