Although immaturity of the liver and synthesis of monohydroxy bile acids have been implicated as pathogenic factors in neonatal cholestasis, there is no direct evidence to show that these bile acids induce cholestasis in the newborn. In the present investigation, we compared the effects of lithocholic acid (LCA) injection on bile flow in suckling (2-week-old) and adult (12-week-old) guinea pigs. Bile flow was not modified by LCA in 2-week-old animals, but it was reduced by 50 to 80% in the adults, the decrease being dose-dependent. In the newborn, the injected LCA was mainly secreted in bile (>go%), while in the adults it was distributed between the liver and bile. The percentage of biliary bile acids (as determined by gas-liquid chromatography) in the two groups was similar before and after LCA injection. Morphologic lesions characteristic of LCAinduced cholestasis were observed only in the adult guinea pigs. This study demonstrates that the newborn guinea pig is less susceptible to cholestasis induced by 90 to 180 pmoles per kg body weight of lithocholate and that, in the neonatal liver, there is no defect in the transport of this bile acid from blood to bile.
There is agreement among various investigators that, in newborn animals and in man, serum bile acid levels are age-dependent and significantly higher during the neonatal period than during adulthood (1-4). This hypercholemia may result not only from perturbations in hepatic hemodynamics (Watkins, J. B. et al., International Bile Acid Meeting, October 1982, Abstract) but also from decreased liver cell uptake, transport or excretion, leading to a possible reduction in bile flow (5-8). Thus, it has been proposed that the newborn is in a state of "physiologic cholestasis" (3, 7), because of some immaturity of the processes involved in bile acid metabolism. On the other hand, the persistence of a fetal pattern of synthesis of cholestatic monohydroxy bile acids has been implicated in the initiation or perpetuation of liver disease (e.g., cholestasis) in the neonatal period (9-12). High concentrations of these bile acids have been observed in the meconium, suggesting their synthesis during fetal life (9). Lithocholic acid (LCA) is the principal monohydroxy bile acid normally found in small amounts