Bile salts and liver disease in childhood

Summary Recognition of neonatal liver disease has been heavily dependent on the occurrence of jaundice. In most instances the jaundice is related to specific disturbances in bilirubin transport and other tests of liver function are normal. In contrast, hepatitis and other liver diseases not specifically affecting bilirubin transport often go undetected unless jaundice occurs. The development of practical methods for the estimation of bile acids in serum has permitted an evaluation of hepatic excretory function in neonates and children independent of bilirubin excretion. Since bile acid excretion by the liver each day greatly exceeds bilirubin excretion it was not surprising to find that elevations in serum bile acids occur regularly in anicteric hepatitis. Because the excretion of bile acids generates canalicular bile flow a reduction in the capacity to excrete bile acids intimates the presence of cholestasis. Early cholestasis is not associated with hyperbilirubinaemia but as cholestasis becomes more severe, jaundice occurs and the possibility of biliary atresia arises in neonates. Serum bile acid patterns in neonates being evaluated for biliary atresia indicate two distinctive patterns. Those infants with severe cholestasis and patent bile ducts usually have pre-dominantly cholic acid in serum. This observation is consistent with the bile acid patterns found in intrahepatic and extrahepatic cholestasis occurring in adult life. Infants found to have extrahepatic biliary atresia have marked elevations in the proportion of chenodeoxycholate in serum. Since elevations of chenodeoxycholate in serum are associated with hepatitis, the findings are consistent with the view that extrahepatic atresia is a rare sequalae of hepatitis. Studies of bile acid metabolism and excretion give promise of providing further insight on the pathogenesis of cholestatic liver disease.