High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis

Am J Gastroenterol. 2001 May;96(5):1558-62. doi: 10.1111/j.1572-0241.2001.03777.x.

Abstract

Objectives: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alkaline Phosphatase / blood
  • Bilirubin / blood
  • Cholangitis, Sclerosing / blood
  • Cholangitis, Sclerosing / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Serum Albumin / analysis
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Ursodeoxycholic Acid / administration & dosage*
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Serum Albumin
  • Ursodeoxycholic Acid
  • Alkaline Phosphatase
  • Bilirubin