ETIOLOGY OF GROWTH FAILURE IN BILIARY ATRESIA

描述（改编自应用程序） 这项建议的目的是确定儿童生长不良的基础 胆道闭锁（BA），并确定这些患者是否可能 从补充生长的合成代谢和生长促进作用中受益 激素和/或补充营养。BA是新生儿肝脏疾病。 虽然外科手术方法试图纠正解剖学问题， 这些儿童通常不能充分成长。70%需要肝脏 移植和最常见的移植指征是穷人 增长大多数作者将生长不良归因于热量不足， 厌食、吸收不良和能量需求增加的综合作用， 慢性肝病这些病人有生长障碍 胰岛素样生长因子（GH-IGF）轴。他们增加了胰岛素， 生长激素升高，IGFBP-1升高，IGF-I降低， IGFBP-3。这种模式的干扰可以看到无论是营养不良或生长激素 阻力因为对这两种疾病的医学治疗 不同的是，我们认为重要的是要确定患者的可能性， 在设计长期治疗方案之前， 改善BA患者生长的干预性试验。 假设： 1. BA儿童的生长障碍是由于：a）部分生长 激素抵抗，导致低循环水平的胰岛素样 生长因子I（IGF-1）和胰岛素样生长因子结合蛋白-3 （IGFBP-3）和/或B）缺乏足够的卡路里，导致相同的模式， GH-lGF轴的扰动。 2.用重组人肝细胞癌治疗儿童胆道闭锁 生长激素（rhGH）或补充营养早期的过程中， 肝脏疾病将纠正GH-IGF轴的改变。 具体目标： 1.确定BA儿童是否对rhGH有反应， IGF-I对治疗的反应 2.确定BA儿童是否对补充营养有反应， 通过响应于治疗的IGF-1的增加来确定 这项研究的目的是制定战略，以改善增长， 孩子们BA我们假设IGF-I会对补充rhGH产生反应， 营养或两者。激素反应可以在五天内建立 住院在我们的一般临床研究单位和营养 可以在四周的鼻饲期间建立反应。的 这项研究的结果将提供一个长期的基础 干预性试验

DESCRIPTION (adapted from the application) The aim of this proposal is to determine the basis of poor growth for children with biliary atresia (BA) and to ascertain if these patients are likely to benefit from the anabolic and growth promoting effects of supplemental growth hormone and/or supplemental nutrition. BA is a neonatal liver disorder. Although surgical approaches have attempted to correct the anatomic problem, these children typically fail to grow adequately. Ultimately 70% require liver transplantation and the most common indication for transplantation is poor growth. Most authors have attributed poor growth to inadequate calories due to a combination of anorexia, malabsorption and increased energy needs resulting from chronic liver disease. These patients have a disturbance of the growth hormone-insulin-like growth factor (GH-IGF) axis. They have increased insulin, increased growth hormone, increased IGFBP-1, depressed IGF-I and depressed IGFBP-3. This pattern of disturbance can be seen with either malnutrition or GH resistance. Because the medical therapy for these two entities is vastly different, we think it is important to determine the likelihood that patients may benefit from one or both therapies before designing a long-term interventional trial to improve growth for patients with BA. Hypotheses: 1. Growth failure in children with BA is either due to: a) partial growth hormone resistance, which results in low circulating levels of insulin-like growth factor I (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) and/or b) lack of sufficient calories leading to the same pattern of disturbance of the GH-lGF axis. 2. Treatment of children with biliary atresia with either recombinant human growth hormone (rhGH) or supplemental nutrition early in the course of the liver disease will correct the alterations of the GH-IGF axis. Specific Aims: 1. Determine if children with BA respond to rhGH as determined by an increase of IGF-I in response to therapy 2. Determine if children with BA respond to supplemental nutrition as determined by an increase of lGF-1 in response to therapy The purpose of this study is to develop strategies to improve growth for children with BA. We hypothesize that IGF-I will respond to supplemental rhGH, nutrition or both. The hormonal response can be established during a five-day hospitalization in our general clinical research unit and the nutritional response can be established during a four-week nasogastric feeding period. The results of this study will provide the foundation for a long-term interventional trial.