Plasma oxysterols in normal and cholestatic children as indicators of the two pathways of bile acid synthesis

Background: No information is available on the hepatic and extrahepatic pathways of bile acid synthesis in normal children and in pediatric cholestatic liver diseases. Methods: To explore the changes of the two pathways of bile acid synthesis during development, plasma concentrations of 7α-hydroxycholesterol and 27-hydroxycholesterol were measured in 50 healthy children (1 month-14 years) and compared to 18 adult controls. We also measured plasma oxysterols in 31 patients with pediatric cholestatic liver disease. Results: A progressive increase of plasma concentrations of both 27-hydroxycholesterol and 7α-hydroxycholesterol was found with age. In children with cystic fibrosis-associated liver disease plasma concentrations of 27-hydroxycholesterol were significantly lower compared to age-matched controls (5.6 ± 0.5 vs. 12.8 ± 1.1 μg/dl; p < 0.001) and paralleled significantly lower concentrations of total cholesterol. In infants with biliary atresia plasma concentrations of 27-hydroxycholesterol were significantly higher compared to age-matched controls (8.8 ± 0.8 vs. 4.4 ± 0.6 μg/dl, p < 0.001) paralleling significantly higher concentrations of total cholesterol while 7α-hydroxycholesterol resulted significantly lower (1.2 ± 0.2 vs. 2.3 ± 0.3 μg/100 mg of total cholesterol; p = 0.011). Conclusions: Our data suggest that both pathways of bile acid synthesis reach a state of maturity only after the age of 4 years and are significantly influenced also in children by liver function and intestinal absorption of cholesterol. © 2008 Elsevier B.V. All rights reserved.