Advertisement

Comprehensive study of the biliary bile acid composition of patients with cystic fibrosis and associated liver disease before and after UDCA administration

Authors

  • Dr. Michiko Nakagawa,

    1. Clinical Mass Spectrometry Laboratories, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229–2899
    Search for more papers by this author
    • Sabbatical from the Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.

  • Carla Colombo,

    1. Department of Pediatrics, University of Milan, Milan, Italy
    Search for more papers by this author
  • Kenneth D. R. Setchell Ph.D.

    Associate Professor of Pediatrics, Director, Corresponding author
    1. Clinical Mass Spectrometry Laboratories, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229–2899
    • Clinical Mass Spectrometry, Division of Pediatrics, Children's Hospital Medical Center, Elland and Bethesda avenues, Cincinnati, OH 45229–2899
    Search for more papers by this author

Abstract

The biliary bile acid composition was determined for patients with cystic fibrosis and associated liver disease before and after the administration of ursodeoxycholic acid (10 to 15 mg/kg body wt/day). Bile acids were analyzed by fast atom bombardment ionizationmass spectrometry, high performance liquid chromatography and gas chromatography-mass spectrometry after individual bile acids were separated according to their mode of conjugation using the lipophilic anion exchanger, diethylaminohydroxypropyl Sephadex LH-20. More than 50 individual bile acids were identified in the bile of cystic fibrosis patients and these acids were predominantly secreted as glycine and taurine conjugates. Small proportions (<8% of the total) of unconjugated and sulfate conjugates were present. Of interest was the identification of two side-chain–elongated (C25) bile acids, homocholic and homochenodeoxycholic acids. After ursodeoxycholic acid was administered, duodenal bile became enriched with the conjugated species of ursodeoxycholic acid (accounting for 11.9% to 32.5% of the total biliary bile acids), but to a lesser extent than reported previously for patients with other liver diseases or gallstones who received comparable doses of ursodeoxycholic acid, and this presumably occurs because of bile acid malabsorption that is a feature of cystic fibrosis. The mean glycine/taurine ratio increased from 2.4 before ursodeoxycholic acid administration to 5 after ursodeoxycholic acid administration even though these patients also received taurine. Despite the relatively low enrichment of the bile by ursodeoxycholic acid, biochemical indices of liver function all improved in these patients after ursodeoxycholic acid administration. (HEPATOLOGY 1990;12:322–334).

Ancillary