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