Abstract
Biliary lipid composition, standard liver function tests, serum lipids and faecal fat excretion were studied in 15 children with chronic intrahepatic cholestasis (severe intrahepatic cholestasis, n=6; paucity of intralobular bile ducts, n=4; benign recurrent cholestasis, n=5) and compared to 15 children without gastrointestinal diseases. Severe and benign intrahepatic cholestasis were associated with normal or moderately elevated serum lipids. Biliary lipid concentrations were extremely reduced, bile acid concentrations were below the critical micellar concentration. This may account for the high incidence of gallstone formation in these patients. Remission periods in patients with benign recurrent cholestasis were not followed by complete normalisation of biliary lipid concentrations, indicating a primary defect in hepatic excretory function. Children with paucity of intralobular bile ducts showed markedly increased serum lipids, but only a two-fold reduction in biliary lipid concentrations. Cholic acid was the predominant bile acid in bile of all cholestatic children even during remission. Neither increased levels of monohydroxy bile acids nor unusual bile acids could be identified in notable amounts.
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Alagille D, Odievre M, Gautier M, Dommergues JP (1975) Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental and sexual development and cardiac murmur. J Pediatr 86:63–71
Alagille D, Odievre M (1979) Liver and biliary tract disease in children. John Wiley and Sons, New York
Bartlett GR (1959) Phosphorus assay in column chromatography. J Biol Chem 234:466–468
Beaudoin M, Feldmann G, Erlinger S, Benhamou J-P (1973) Benign recurrent cholestasis. Digestion 9:49–65
Becker M, Ruoff H-J, Rotthauwe HW (1980) Cyclic AMP in pancreatic and biliary secretion of children with chronic intrahepatic cholestasis and cystic fibrosis. Eur J Pediatr 134:217–225
Becker M, von Bergmann K, Rotthauwe HW, Leiss O (1984) Effects of phenobarbital on biliary lipid metabolism in children with chronic intrahepatic cholestasis. Eur J Pediatr 143:41–44
Collins DM, Shannon FT, Campbell CB (1981) Bile acid metabolism in mild arteriohepatic dysplasia. Aust NZ J Med 11:48–51
Day RC, Harry DS, Owen JS, Foo AY, McIntyre N (1979) Lecithin-cholesterol acyltransferase and the lipoprotein abnormalities of parenchymal liver disease. Clinical Science 56:575–583
Deleze G, Paumgartner G (1977) Bile acids in serum and bile of infants with cholestatic syndromes. Helv Paediatr Acta 32:29–38
Einarsson K, Hellstrom K, Schersten T (1975) The formation of bile acids in patients with liver cirrhosis. Scand J Gastroenterol 10:299–304
Endo T, Uchida K, Amuro Y, Higashino K, Yamamura Y (1979) Bile acid metabolism in benign recurrent intrahepatic cholestasis. Gastroenterology 76:1002–1006
Eyssen H, Parmentier G, Compernolle F, Boon J, Eggermont E (1972) Trihydroxycoprostanic acid in the duodenal fluid of two children with intrahepatic bile duct abnormalities. Biochim Biophys Acta 273:212–221
Grundy SM, Metzger AL (1972) A physiological method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology 62:1200–1217
Grundy SM, Ahrens EH jr, Miettinen TA (1965) Quantitative isolation and gas-liquid chromatographic analysis of total fecal bile acids. J Lipid Res 6:397–410
Javitt NB (1975) Current status of cholestasis induced by monohydroxy bile acids. In: Goresky CA, Fisher MM (eds) Jaundice. Plenum Press, New York, pp 401–409
Javitt NB, Morrissey KP, Siegel E, Goldberg H, Gartner LM, Hollander M, Kok E (1973) Cholestatic syndromes in infancy: diagnostic value of serum bile acid pattern and cholestyramine administration. Pediatr Res 7:110–125
Kesaniemi YA, Salaspuro MP, Vuoristo M, Miettinen TA (1982) Biliary lipid secretion in chronic cholestatic liver disease. Gut 23:931–938
Linarelli LG, Williams CN, Phillips MJ (1972) Byler's disease: fatal intrahepatic cholestasis. J Pediatr 81:484–492
Linarelli LG, Hengstenberg FH, Drash AL (1973) Effect of phenobarbital on hyperlipemia in patients with intrahepatic and extrahepatic cholestasis. J Pediatr 83:291–299
Mashige F, Imai K, Osuga T (1976) A simple and sensitive assay of total serum bile acids. Clin Chim Acta 70:79–86
McIntyre N, Calandra S, Pearson AJG (1974) Lipid and lipo-protein abnormalities in liver disease: the possible role of lecithin: cholesterol acyltransferase deficiency. Scand J Clin Lab Invest [Suppl 33] 137:115–120
McIntyre N, Harry DS, Pearson AJG (1975) The hypercholesterolaemia of obstructive jaundice. Gut 16:379–391
Miettinen TA, Siurula M (1971) Micellar solubilization of intestinal lipids and sterols in gluten enteropathy and liver cirrhosis. Scand J Gastroenterol 6:527–535
Mok HYI, von Bergmann K, Grundy SM (1978) Effects of interruption of enterohepatic circulation on biliary lipid secretion in man. Dig Dis Sci 28:1067–1075
Nair PP, Gordon M, Reback J (1967) The enzymatic cleavage of the carbonhydrogen bound in 3-alpha, 7-alpha, 12-alpha-trihydroxy-5-beta-cholan-25-olylglycine. J Biol Chem 242:7–11
Nilsson S, Schersten LS (1969) Importance of bile acids for phospholipid secretion into human hepatic bile. Gastroenterology 57:525–532
Odievre M, Gautier M, Hadchouel M, Alagille D (1973) Severe familial intrahepatic cholestasis. Arch Dis Child 48:806–812
Paumgartner G, Horak W, Probst P, Grabner G (1971) Effect of phenobarbital on bile flow and bile salt excretion in the rat. Naunyn Schmiedeberg's Arch Pharmacol 270:98–102
Poley JR (1975) Fat digestion and absorption in lipase and bile acid deficiency. In: Rommel K, Boehmer R (eds) Lipid absorption: biochemical and clinical aspects. MTP Press Ltd, Lancester, pp 151–199
Quarfordt SH, Jakoi L (1973) Alterations of hepatic cholesterol synthesis in rats by lecithin and lecithin cholesterol mesophase infusions (abstract). Gastroenterology 65:566
Rotthauwe HW, Becker M, Bosch Ch (1981) Progressive intrahepatische Cholestase. Monatsschr Kinderheilkd 129:515–520
Sabesin SM (1982) Cholestatic lipoproteins—their pathogenesis and significance. Gastroenterology 83:704–709
Sachs L (1974) Angewandte Statistik. Springer, Heidelberg New York
Salen G, Nicolau G, Shefer S, Mosbach EH (1975) Hepatic cholesterol metabolism in patients with gallstones. Gastroenterology 69:676–684
Schlenk H, Gellermann JL (1960) Esterification of fatty acids with diazomethane on a small scale. Anal Chem 32:1412–1414
Schwartz CC, Almond HR, Vlahcevic ZR, Swell L (1979) Bile acid metabolism in cirrhosis. V. Determination of biliary lipid secretion rates in patients with advanced cirrhosis. Gastroenterology 77:1177–1182
Stark H (1968) Benign recurrent cholestasis in a child. Pediatrics 41:636–639
Stiehl A, Thaler MM, Admirand WH (1972) The effects of phenobarbital on bile salts and bilirubin in patients with intrahepatic and extrahepatic cholestasis. New Engl J Med 286:858–861
Summerfield JA, Scott J, Berman M, Ghent C, Bloomer JR, Berk PD, Sherlock S (1980) Benign recurrent intrahepatic cholestasis: studies of bilirubin kinetics, bile acids and cholangiography. Gut 21:154–160
Switzer S (1967) Plasma lipoproteins in liver disease. I. Immunologically distinct low-density lipoproteins in patients with biliary obstruction. J Clin Invest 46:1855–1866
Talalay P (1960) Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:114–143
Van Berge Henegouwen GP, Allan RN, Hofmann AF, Yu PYS (1977) A facile hydrolysis-solvolysis procedure for conjugated bile acid sulfates. J Lipid Res 18:118–122
Van Berge Henegouwen GP, Ferguson DR, Hofmann AF, de Pagter AGF (1978) Familial and non-familial benign recurrent cholestasis distinguished by plasma disappearance of indocyanine green but not cholylglycine. Gut 19:345–350
Van Berge Henegouwen GP, Brandt K-H, Ruben AT, Schalm SW, Taal B (1982) High frequency of lithogenic bile in primary biliary cirrhosis. Neth J Med 25:89–93
Van de Kamer JH, ten Bokkel Huinink H, Weijers HA (1949) A rapid method for the determination of fat in faeces. J Biol Chem 177:347–355
Vlahcevic YR, Bell CC, Juttijudata P, Swell L (1972) Bile-rich duodenal fluid as an indicator of biliary lipid composition and its applicability to detection of lithogenic bile. Am J Dig Dis 9:797–802
Vlahcevic YR, Yoshida T, Juttijudata P, Bell CC, Swell L (1973) Bile acid metabolism in cirrhosis. III. Biliary lipid secretion in patients with cirrhosis and its relevance to gallstone formation. Gastroenterology 64:298–303
Watson GH, Miller B (1973) Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child 48:459–466
Weber A, Roy C (1972) The malabsorption associated with chronic liver disease in children. Pediatrics 50:73–83
Williams CN, Kaye R, Baker L, Hurwitz R, Senior JR (1972) Progressive familial cholestatic cirrhosis and bile acid metabolism. J Pediatr 81:493–500
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Becker, M., von Bergmann, K., Rotthauwe, H.W. et al. Biliary lipid metabolism in children with chronic intrahepatic cholestasis. Eur J Pediatr 143, 35–40 (1984). https://doi.org/10.1007/BF00442745
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DOI: https://doi.org/10.1007/BF00442745