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.
