IGF-I TREATMENT/EXTRAHEPATIC BILIARY ATRESIA OR ALAGILLE SYNDROME

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Growth Hormone (GH) and insulin-like growth factor-1 (IGF-1) are anabolic hormones which are necessary for normal growth. We previously showed that children with chronic liver disease have low serum concentrations of IGF-1 despite elevated circulating GH levels and that growth-retarded children with Alagille syndrome or biliary atresia and progressive liver disease are insensitive to GH. As a logical extension of our initial studies examining response to GH in children with chronic liver disease, we are initiating a Phase 2 study sponsored under IND #39380 to examine the effect of rhIGF-1 on chronic liver disease and insensitivity to GH. We will study 6 infants 0.5 to 1 year, since this group comprises the subset of children with increased risk of mortality and morbidity following OLT. The goal of this proposal is to test the hypothesis that treatment with IGF-1 promotes anabolism in children with biliary atresia awaiting Orthotopic Liver Transplantation. IGF-1 will be administered at a dose of 80 g/kg twice daily by subcutaneous injection. To assess the effect of 5 d treatment with IGF-1 on nitrogen balance, we will measure total nitrogen excretion from combined urine and stool collection at baseline and with IGF-1 treatment.