Incomplete response to ursodeoxycholic acid in primary biliary cirrhosis: is a double dosage worthwhile?
OBJECTIVE
The aim of this study was to assess the safety and efficacy of high-dose ursodeoxycholic acid (UDCA, 28-32 mg/kg/day) in patients with primary biliary cirrhosis (PBC) who had shown an incomplete response to the standard dose (13-15 mg/kg/day).


METHODS
A total of 25 patients with PBC who had been on UDCA (13-15 mg/kg/day) therapy for 24-141 months and had shown persistent elevation of ALP activity at least two times the upper limit of normal were enrolled. The dose of UDCA was increased to 30 (28-32) mg/kg/day and given for 1 yr.


RESULTS
A significant but marginal improvement in serum ALP activity (707+/-52 vs 571+/-32, p = 0.001) was noted at 1 yr of treatment with high-dose UDCA. However, levels of total bilirubin (1.1+/-0.2 vs 1.0+/-0.2, p = 0.1), AST (58+/-9 vs 54+/-1, p = 0.1), albumin (4.1+/-0.7 vs 4.0+/-0.08, p = 0.1), or Mayo risk score (4.13+/-0.3 vs 4.12+/-0.3, p = 0.2) remained essentially unchanged. Normalization of liver tests did not occur in any patient, and adverse events were not recorded in any case.


CONCLUSIONS
Although UDCA at a dose of 28-32 mg/kg/day is well tolerated, this dosage does not seem to benefit most patients with PBC responding incompletely to a dose of 13-15 mg/kg/day. The results of this pilot study would seem to discourage further controlled trials of high-dose UDCA in suboptimal responders to the standard dose of UDCA.
Angulo
P
P
Division of Gastroenterology and Hepatology, Mayo Clinic Foundation, Rochester, Minnesota 55905, USA.
Jorgensen
R A
RA
Lindor
K D
KD
D000328:Adult; D000368:Aged; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid