title: Ursodeoxycholic acid improves the hepatic metabolism of essential fatty acids and retinol in children with cystic fibrosis.
abstract: OBJECTIVE
  Several clinical trials of ursodeoxycholic acid (UDCA) have shown improvement of liver-function test results in cystic fibrosis (CF) with liver disease; however, there is no evidence that the long-term course will be affected. In view of the observations that UDCA can change the lipid profile and that patients with CF and liver disease are more likely to have essential fatty acid (EFA) deficiency, we elected to examine changes in the lipid profile and in the status of fat-soluble vitamins in response to UDCA.
  
  
  METHODS
  Nineteen children with CF and liver dysfunction were recruited for a double-blind, crossover study of 1 year's duration, followed by treatment of the entire group. UDCA was administered at a dosage of 15 mg/kg per day, which, in the absence of a 50% decrease of alanine transaminase or aspartate transaminase or both within 2 months, was increased to 30 mg/kg per day.
  
  
  RESULTS
  At entry, all patients had biochemical evidence of EFA deficiency. The lipid profiles during an average period of 25 months of follow-up showed a significant decrease in triglycerides (p <0.002), cholesterol (p <0.02), and total fatty acids (p <0.006). In addition, UDCA therapy led to an improvement in EFA status, as indicated by an increase (p <0.05) in the n-6 fatty acid concentration and a reduction (p <0.04) in the 20:3n-9/20:4n-6 fatty acid ratio. Although no change in vitamin E levels was observed, retinol metabolism was altered. There was an increase (p <0.02) in the unesterified retinol/retinol binding protein molar ratio in the absence of a difference in retinol binding protein concentration. Furthermore, retinyl esters, which normally account for less than 3% of circulating retinol, decreased (p <0.05) from 13.7% +/- 3.6% to 8.1% +/- 1.7%.
  
  
  CONCLUSIONS
  This study confirms that UDCA alters lipoprotein metabolism and shows that it improves the EFA and retinol status of patients with CF and liver disease.
authors.affiliation: Gastroenterology and Nutrition Service, Department of Pediatrics, Hôpital Ste-Justine, Université de Montréal, Québec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Lepage
authors.forename: K
authors.initials: K
authors.lastname: Paradis
authors.forename: F
authors.initials: F
authors.lastname: Lacaille
authors.forename: L
authors.initials: L
authors.lastname: Sénéchal
authors.forename: N
authors.initials: N
authors.lastname: Ronco
authors.forename: J
authors.initials: J
authors.lastname: Champagne
authors.forename: C
authors.initials: C
authors.lastname: Lenaerts
authors.forename: C C
authors.initials: CC
authors.lastname: Roy
authors.forename: A
authors.initials: A
authors.lastname: Rasquin-Weber
mesh_terms: D000293:Adolescent; D002648:Child; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005228:Fatty Acids, Essential / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D014801:Vitamin A / Q000378:metabolism*; D014815:Vitamins / Q000378:metabolism
chemical_list: D002756:Cholagogues and Choleretics; D005228:Fatty Acids, Essential; D014815:Vitamins; D014801:Vitamin A; D014580:Ursodeoxycholic Acid