High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis.
OBJECTIVE
To assess the tolerability and efficacy of high-dose (25-30 mg/kg per day) ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC).


METHODS
Thirty patients with PSC were enrolled in this pilot study and treated for 1 yr. Changes in the Mayo risk score at 1 yr of treatment and projected survival at 4 yr were compared with that observed in patients randomized to placebo (n = 52) or UDCA (n = 53) at a dose of 13-15 mg/kg per day.


RESULTS
A marked improvement in serum alkaline phosphatase activity (1265+/-172 vs 693+/-110 U/L, p < 0.001), AST (161+/-037 vs 77+/-13 U/L, p = 0.001), albumin (4.0+/-0.1 vs 4.2+/-0.1 g/dl, p = 0.03), and total bilirubin (1.6+/-0.3 vs 1.3+/-0.2 mg/dl, p = 0.1) occurred at 1 yr of therapy with high-dose UDCA. Changes in the Mayo risk score after 1 yr of treatment were significantly different among the three groups (p < 0.001), and these changes would be translated into a significantly different expected survival at 4 yr (p = 0.05). This expected survival at 4 yr was significantly different between placebo and the dose of 25-30 mg/kg per day (p = 0.04), but not between placebo and the dose of 13-15 mg/kg per day (p = 0.4). High-dose UDCA was well tolerated.


CONCLUSIONS
UDCA at a dose of 25-30 mg/kg per day may be of benefit for patients with PSC, and this regimen deserves further evaluation in a long-term, randomized, placebo-controlled trial.
Harnois
D M
DM
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Angulo
P
P
Jorgensen
R A
RA
Larusso
N F
NF
Lindor
K D
KD
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012709:Serum Albumin / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000627:therapeutic use
D012709:Serum Albumin; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D001663:Bilirubin