GROWTH-HORMONE INSENSITIVITY IN CHILDREN WITH BILIARY ATRESIA

Malnutrition is a critical predictor of mortality and morbidity in chi ldren with biliary atresia who undergo orthotopic liver transplantatio n. Growth hormone (GH) enhances nitrogen retention in patients with ch ronic obstructive lung disease, sepsis, and in fasted adult volunteers . The goal of this study was to assess the acute response to recombina nt human GH (rhGH) treatment in children with biliary atresia to deter mine whether GH therapy was likely to improve pretransplant nutritiona l status. Five children, aged 10-32 months, with biliary atresia and p ersistent cholestasis despite surgical attempts to reestablish bile fl ow, were studied. All five children had portal hypertension, conjugate d hyperbilirubinemia, and decreased serum albumin concentrations. Leng th, weight, and growth velocity were decreased in all five children. D espite adequate energy and protein intake, fat stores were depleted in all five subjects, and somatic protein stores were diminished in all except one child. Baseline serum concentration of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were low (8.4 +/- 2 ng/ml and 0.2 +/- 0.1 mg/l respectively). In the four children who completed the study, serum IGF-I and IGFBP-3 levels did not change aft er treatment with rhGH (0.1 mg/kg/day) for 4 days. Our findings indica te that children with biliary atresia awaiting liver transplantation a re insensitive to GH and that treatment with GH is unlikely to promote anabolism. A rationale exists for examining the effect of treatment w ith IGF-I, which mediates the anabolic effects of GH.