Low-Dose versus High-Dose Ursodeoxycholic Acid in Cystic Fibrosis-Related Cholestatic Liver Disease Results of a Randomized Study with 1-Year Follow-up

Abstract

VanBerge-Henegouwen GP. Low-dose versus high-dose ursodeoxycholic acid in cystic fibrosis-related cholestatic liver disease. Results of a randomized study with 1-year follow-up. Scand J Gastroenterol 1997;32:369-373.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 y-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. confirmed by the presence of typical pulmonary and digestive abnormalities and a sweat chloride concentration of more than 60 mmol/l. The presence of cholestatic liver disease was documented at separate occasions at least 3 months apart and Scand J Gastroenterol Downloaded from informahealthcare.com by University of Pennsylvania on 04/13/15 For personal use only. Scand J Gastroenterol Downloaded from informahealthcare.com by University of Pennsylvania on 04/13/15 For personal use only. Scand J Gastroenterol Downloaded from informahealthcare.com by University of Pennsylvania on 04/13/15 For personal use only.

Hepatobiliary complications of cystic fibrosis

“…Prospective clinical trials of UDCA, at doses of 10 to 20 mg/kg/d for 6 to 12 months, have shown significant improvements in serum liver enzyme levels in pediatric patients with CF liver disease [44,45]. However, higher doses (20 mg/kg/d) may be necessary in the treatment of CF liver disease, compared with other forms of cholestasis [46,47]. In a 2-year uncontrolled study, UDCA therapy improved the liver histology, with less inflammation and bile duct proliferation, in seven of 10 patients with CFrelated liver disease [48].…”

Ursodeoxycholic acid in cholestatic liver disease: Mechanisms of action and therapeutic use revisited

“…A higher dosage of UDCA (20 mg/kg/d) appears to be more effective than a lower dosage (10 mg/ kg/d) because the intestinal absorption of UDCA and, as a consequence, enrichment of bile with UDCA may be impaired when pancreatic insufficiency is present. 52 UDCA appears to be an effective and safe treatment in cholestatic liver disease of cystic fibrosis. However, its effect on survival has yet to be proven.…”

Use of ursodeoxycholic acid in patients with liver disease

“…In a randomized trial, UDCA (15 mg/kg/d) improved clinical and biochemical parameters as well as liver histology [39]. A subsequent study showed that a dosage of 20 mg/kg/d provided greater improvement of liver tests than a lower dose [40]. Further studies are necessary to determine the effect of UDCA in disease progression and long-term outcomes in patients with CF-associated liver disease.…”