Impact of chronic liver disease and liver transplantation on total branched chain amino acid requirements in children

Current WHO/FAO/UNU recommendations for branched chain amino acids (BCAA) requirements are based on nitrogen balance studies conducted in 10--12 year old children. No studies have directly measured BCAA requirements in healthy children or in children with chronic disease. The primary objective of our studies was to directly measure total BCAA requirements in healthy children and children with chronic liver disease using the minimally invasive indicator amino acid oxidation (IAAO) technique. The model used in these studies was to feed the BCAA in proportions that mimic the content in egg protein in order to minimize the potential interactive effects of the individual BCAA on assessment of requirement. Total BCAA requirements were determined in healthy children and in children with chronic liver disease in the pre-and-post liver transplant period using L[1-13C]phenylalanine as the oral isotope tracer.; Five healthy school-aged children and five children with mild chronic cholestatic liver disease were studied at graded levels of the total BCAA. Mean total BCAA requirement (EAR) and upper 95% CI (RDA) in these children was 147 and 191.5 mg/(kg·d), respectively. Mean total BCAA requirement (EAR) and upper 95% CI (RDA) in children with mild chronic cholestatic liver disease was 209 and 280 mg/(kg·d), respectively. In order to identify potential underlying mechanisms responsible for this increase in requirement, we measured L-[1-13C]leucine oxidation in the fed and post-absorptive state in healthy children and children with mild chronic cholestatic liver disease. Leucine oxidation was significantly higher in the post-absorptive state in children with mild chronic cholestatic liver disease.; In order to identify the impact of liver transplantation, we also studied total BCAA requirements in five children who have undergone orthotopic liver transplantation (OLT). The mean total BCAA requirements and RDA (upper 95% confidence limit) in children who have undergone OLT was significantly higher (175 and 211 mg/(kg·d)) than requirements in healthy children. These results suggest that the impact of liver transplantation in children with mild chronic cholestatic liver disease is to restore requirements towards those of healthy children, although requirements remain significantly higher in the post-transplant period (p < 0.05).