URSODEOXYCHOLIC ACID IMPROVES THE HEPATIC-METABOLISM OF ESSENTIAL FATTY-ACIDS AND RETINOL IN CHILDREN WITH CYSTIC-FIBROSIS

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-te rm course will be affected. In view of the observations that UDCA can change the lipid profile and that patients with CF and liver disease a re more likely to have essential fatty acid (EFA) deficiency, we elect ed to examine changes in the lipid profile and in the status of fat-so luble vitamins in response to UDCA. Methods: Nineteen children with CF and liver dysfunction were recruited for a double-blind, crossover st udy of 1 year's duration, followed by treatment of the entire group. U DCA was administered at a dosage of 15 mg/kg per day, which, in the ab sence of a 50% decrease of alanine transaminase or aspartate transamin ase or both within 2 months, was increased to 30 mg/kg per day. Result s: 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), cholestero l (p < 0.02), and total fatty acids (p < 0.006). In addition, UDCA the rapy 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 vit amin E levels was observed, retinol retinol/retinol binding protein mo lar ratio in the absence of a difference in retinol binding protein co ncentration. Furthermore, retinyl esters, which normally account for l ess 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 al ters lipoprotein metabolism and shows that it improves the EFA and ret inol status of patients with CF and liver disease.