Low-dose versus high-dose ursodeoxycholic acid in cystic fibrosis-related cholestatic liver disease - Results of a randomized study with 1-year follow-up

Background: Ursodeoxycholic acid (UDCA) is beneficial in cholestasis related to cystic fibrosis (CF). High-dose treatment has been recommended to compensate for bile salt malabsorption. We compared the results of low-dose (10 mg/kg/day) and high-dose (20 mg/kg/day) UDCA treatment on liver biochemistry after 3 and 12 months' treatment. Methods: Thirty CF patients (age > 5 years) with biochemical cholestasis and compensated liver disease were randomized for low-dose (n = 17) or high-dose (n = 13) UDCA. Baseline clinical variables were comparable. Results: After 1 year one patient had died of liver failure (low dose), and three had dropped out because of pruritus (one in each group) or personal choice (low dose). In the high-dose group improvement in gamma-glutamyl transferase values was more pronounced after 3 months and 1 year (P <0.004), and improvement of alanine aminotransferase was better after 1 year (P <0.02). Improvement of alkaline phosphatase and aspartate aminotransferase was comparable. Complete normalization of liver enzymes and bilirubin occurred more often in the high-dose group. Conclusion: High-dose UDCA induces a better response of liver biochemistry values than low-dose UDCA in CF patients with cholestatic liver disease.