Hjf. Vanhoogstraten et al., A RANDOMIZED TRIAL IN PRIMARY BILIARY-CIRRHOSIS COMPARING URSODEOXYCHOLIC ACID IN DAILY DOSES OF EITHER 10 MG KG OR 20 MG/KG/, Alimentary pharmacology & therapeutics, 12(10), 1998, pp. 965-971
Background: Ursodeoxycholic acid (UDCA) prolongs transplantation-free
survival in primary biliary cirrhosis (PBC). However, the optimal ther
apeutic dose has not been established. Aim: To compare the effects of
UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver
biochemistry and biliary UDCA enrichment. Methods: A 6-month multicen
tre randomized open controlled trial was conducted to assess the effec
ts of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation
of 10 mg/kg/day for patients who had not achieved biochemical normali
zation during treatment for at least 6 months with the 10 mg/kg dose.
Clinical and laboratory evaluations were performed at entry and at 3-m
onth intervals. The percentage UDCA in duodenal bile was assessed at e
ntry and at 6 months.Results: Sixty-one patients were enrolled. No sid
e-effects of UDCA were observed. Within the 20 mg/kg/day group signifi
cant decreases were found for alkaline phosphatase (- 8%; P = 0.003),
aspartate aminotransferase (- 11%; P = 0.01), alanine aminotransferase
(- 17%; P < 0.001), gamma-glutamyl transferase (- 34%; P < 0.001), im
munoglobulin M (- 11%; P = 0.002) and cholesterol (- 8.1%; P < 0.001).
In the 10 mg/kg group none of these parameters differed significantly
from baseline. No significant differences between dose groups for sym
ptom scores or serum bilirubin were found. Biliary enrichment with UDC
A increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while rem
aining stable in the 10 mg/kg group. Conclusions: Liver biochemistry i
mproved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose
of 10 mg/kg/day. Both doses were equally well tolerated. These result
s indicate that UDCA 10 mg/kg/day is a suboptimal dose for treating PB
C.