This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biliary atresia is the leading cause of extrahepatic obstructive jaundice in children. First line therapy is Kasai hepatic portoenterostomy to re-establish bile flow; however, affected children experience multiple complications including cholangitis, growth failure, and liver dysfunction, and ultimately require liver transplantation. A multifactor etiology for the growth failure has been proposed including inadequate caloric intake, malabsorption, altered energy metabolism, and worsening liver function. The successes of liver transplantation have not been paralleled by complete reversal of impaired growth. Growth recovery after liver transplantation appears to be related to severity of the pre-transplant growth deficits, thereby suggesting that the greater the growth deficits to be bridged, the less likely to ultimately achieve normal growth. There is an urgency to define and reverse the factors negatively impacting on growth from the time of diagnosis with biliary atresia. Therefore, the hypotheses of this pilot study are that impaired growth in children with biliary atresia receiving nutritional intervention with 150% of recommended caloric intake for age (RDA) still stems from an energy imbalance phenomenon (energy expenditure and losses from malabsorption in excess of caloric intake), and that the imbalance is related to status of liver disease, tumor necrosis factor (TNF), and worsens with advancing chronological age. The study will longitudinally examine the associations between growth status (z-scores for weight, length/height and skinfold anthropometry), energy balance (caloric intake, degree of steatorrhea, resting and total energy expenditure), indices of disease severity (serum bilirubin, bile acids, transaminases, and levels of TNF) over a six-month period in a homogenous sample of children with biliary atresia (aged 3-years) receiving nutrition intervention with 150% of RDA. Resting energy expenditure will be measured using indirect calorimetry. Total energy expenditure and body composition (fat-free mass and percent body fat) will be measured using doubly labeled water (2H218O). The findings may provide a basis for investigating more aggressive approaches to nutrition intervention.
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