Abstract
To clarify the relationship of progressive familial intrahepatic cholestasis (Byler disease) to bile acid metabolism, we analysed, by high performance liquid chromatography, the bile acid composition of serum and bile in seven children with Byler disease and in eight control children with other cholestatic diseases. In serum, total bile acid concentration was increased in patients with Byler disease (0.30±0.05 mmol/l) and in control patients (0.21±0.08 mmol/l). Cholate (C) and chenodeoxycholate (CDC) cornprised the major proportion of total bile acids in patients with Byler disease as in control patients. Hyocholate (HC) was only detected in patients with Byler disease and lithocholate was only present in control children. In bile, total bile acid concentration was very low in patients with Byler disease (1.1±1.4 mmol/l) compared to control patients (88.9±83.2 mmol/l). C and CDC were the major bile acids in control patients, whereas C and HC comprised the major proportion of bile acids in patients with Byler disease. These results suggest the existence of a defect of primary bile acid secretion in Byler disease characterized by the presence of high concentration of bile acids in serum and absence or very low concentration of bile acids in bile.
Similar content being viewed by others
Abbreviations
- C :
-
cholate
- CDC :
-
chenodeoxycholate
- HC :
-
hyocholate
- LC :
-
lithocholate
References
Berthelot P, Erlinger S, Dhumeaux D, Preaux AM (1970) Mechanism of phenobarbitai-induced hypercholeresis in the rat. Am J Physiol 219: 809–813
Boyer JL (1983) Tight junctions in normal and cholestatic liver: does the paracellular pathway have functional significance? Hepatology 3: 614–617
Chobert MN, Bernard O, Bulle B, Lemonnier A, Guellaen G, Alagille D (1989) High hepatic γ-glutamyltrans-ferase (γ-GT) activity with normal serum γ-GT in children with progressive idiopathic cholestasis. J Hepatol 8: 22–25
Clayton PT, Leonard JV, Lawson AM, et al (1987) Familial giant cell hepatitis associated with synthesis of 3β. 7α-Dihydroxy and 3β, 7α, 12α-trihydroxy-5-cholenoic acids. J Clin Invest 79: 1031–1038
Clayton RJ, Iber FL, Ruebner BH, McKusick VA (1969) Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. Am J Dis Child 117: 112–124
Hirata E, Inoue M, Morino Y (1984) Mechanism of biliary secretion of membranous enzymes: bile acids are important factors for biliary occurrence of γ-glutamyltransferase and other hydrolases. J Biochem 96: 289–297
Ichimiya H, Nazer H, Gunasekaran T, Clayton P, Sjövall J (1990) Treatment of chronic liver disease caused by 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Arch Dis Child 65: 1121–1124
Lamri Y, Roda A, Dumont M, Feldmann G, Erlinger S (1988) Immunoperoxidase localisation of bile salts in rat liver cells. Evidence for a role of the Golgi apparatus in bile salt transport. J Clin Invest 82: 1173–1182
Linarelli LG, Williams CN, Phillips MJ (1972) Byler disease: fatal intrahepatic cholestasis. J Pediatr 81: 484–492
Maggiore G, Bernard O, Riely CA, Hadchouel M, Lemonnier A, Alagille D (1987) Normal serum γ-glutamyl-transpeptidase activity identifies groups of infants with idiopathic cholestasis with poor prognosis. J Pediatr 111: 251–252
Meier PJ (1988) Transport polarity of hepatocytes. Sem Liver Dis 8: 293–307
Meier PJ, Meier-Abt AS, Boyer JL (1987) Properties of the canalicular bile acid transport system in rat liver. Biochem J 242: 465–469
Nathanson MH, Boyer JL (1991) Mechanisms and regulation of bile secretion. Hepatology 14: 551–566
Riely CA (1987) Familial intrahepatic cholestatic syndromes. Sem Liver Dis 7: 119–133
Rossi SS, Converse JL, Hofmann AF (1987) High pressure liquid chromatographic analysis of conjugated bile acids in human bile: simultaneous resolution of sulfated and unsulfated lithocholyl amidates and the common conjugated bile acids. J Lipid Res 28: 589–595
Ruetz S, Fricker G, Hugentobler G, Winterhalter K, Kurz G, Meier PJ, (1987) Isolation and characterization of the putative canalicular bile salt transport system of rat liver. J Biol Chem 23: 11324–11330
Sacquet E, Parquet M, Riottot M, et al (1983) Intestinal absorption, excretion, and biotransformation of hyodeoxycholic acid in man. J Lipid Res 24: 604–613
Setchell KDR, Dumaswala R, Colombo C, Ronchi M (1988) Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem 263: 16637–16644
Setchell KDR, Suchy FJ, Weish MB, Zimmer-Nechemia SL, Heubi J, Balistreri WF (1988) {ie428-2 5β-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis}. J Clin Invest 82: 2148–2157
Shoda J, Mahara R, Osuga T, et al (1988) Similarity of unusual bile acids in human umbilical cord blood and amniotic fluid from newborns and in sera and urine from adult patients with cholestatic liver diseases. J Lipid Res 29: 847–858
Stellard F, Watkins JB, Szcezpanik-Van Leeuwen P, Alagille D (1979) Hyocholic acid, an unusual bile acid in Byler disease. Gastroenterology 77: A42
Stieger B, O'Neill B, Meier PJ (1992) ATP-dependent bile-salt transport in canalicular rat liver plasma-membrane vesicles. Biochem J 284: 67–74
Stiehl A, Becker M, Czygan, et al (1980) Bile acids and their sulphated and glucuronidated derivatives in bile, plasma and urine of children with intrahepatic cholestasis: effects of phenobarbital treatment. Eur J Clin Invest 10: 307–316
Suchy FJ, Bucuvalas JC, Novak DA (1987) Determinants of bile formation during development: ontogeny of hepatic bile acid metabolism and transport. Sem Liver Dis 7: 77–84
Tangerman A, Van Schaik A, Van Berge Henegouwen GP (1986) Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects. Clin Chim Acta 159: 123–132
Tazawa Y, Yamada M, Nakagawa M, Konno T, Tada K (1985) Bile acid profiles in siblings with progressive intrahepatic cholestasis: absence of biliary chenodeoxycholate. J Pediatr Gastroenterol Nutr 4: 32–37
Vlahcevic ZR, Juttijudata P, Bell CC Jr, Swell L (1972) Bile acid metabolism in patients with cirrhosis. II. Cholic and chenodeoxycholic acid metabolism. Gastroenterology 62: 1174–1181
Weber AM, Tuchweber B, Yousef I, et al (1981) Severe familial cholestasis in North American Indian children: a clinical model of microfilament dysfunction? Gastroenterology 81: 653–662
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jacquemin, E., Dumont, M., Bernard, O. et al. Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease). Eur J Pediatr 153, 424–428 (1994). https://doi.org/10.1007/BF01983406
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01983406