Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation.
BACKGROUND
The success of orthotopic liver transplantation as treatment for end-stage liver disease has prompted investigation of strategies to maintain or improve nutrition and growth in children awaiting transplantation, because malnutrition is an adverse prognostic factor. The purpose of this study was to evaluate the effect of recombinant human growth hormone therapy on body composition and indices of liver function in patients awaiting transplant.


METHODS
The study was designed as a placebo-controlled, double-blind, crossover trial. Patients received 0.2 U/kg growth hormone, subcutaneously, or placebo daily for 28 days during two treatment periods, separated by a 2-week washout period. Ten patients (mean age, 3.06 +/- 1.15 years; range, 0.51-11.65 years, five men), with extrahepatic biliary atresia (n = 8) or two with Alagille's syndrome (n = 2), with end-stage liver disease, completed the trial while awaiting orthotopic liver transplantation. Height, weight, total body potassium, total body fat, resting energy expenditure, respiratory quotient, hematologic and multiple biochemical profile, number of albumin infusions, insulin-like growth factor-1 and 1, growth hormone binding protein (GHBP), and insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein (IGFBP-3) were measured at the beginning and end of each treatment period.


RESULTS
Growth hormone treatment was associated with a significant decline in serum bilirubin (-34.6 +/- 16.5 mumol/l vs. 18.2 +/- 11.59 mumol/l; p < 0.02) but there was no significant effect on any anthropometric or body composition measurements, or on any biochemical or hematologic parameters.


CONCLUSIONS
These children with end-stage liver disease displayed growth hormone resistance, particularly in relation to the somatomedin axis. Exogenous growth hormone administration may be of limited value in these patients.
Children's Nutrition Research Centre, Royal Children's Hospital, Herston, Queensland, Australia.
R M
RM
Greer
P
P
Quirk
G J
GJ
Cleghorn
R W
RW
Shepherd
D001663:Bilirubin / Q000097:blood; D001823:Body Composition; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008099:Liver / Q000503:physiopathology; D008107:Liver Diseases / Q000503:physiopathology* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D009752:Nutritional Status; D010919:Placebos; D011188:Potassium / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*
D010919:Placebos; D013002:Somatomedins; D019382:Human Growth Hormone; D001663:Bilirubin; D011188:Potassium