Association between reduced levels of alkaline phosphatase and survival times of patients with primary sclerosing cholangitis

Clin Gastroenterol Hepatol. 2013 Jul;11(7):841-6. doi: 10.1016/j.cgh.2012.12.032. Epub 2013 Jan 22.

Abstract

Background & aims: Ursodeoxycholic acid (UDCA) has not been shown to stop progression of primary sclerosing cholangitis (PSC). However, patients with primary biliary cirrhosis treated with UDCA whose levels of alkaline phosphatase (ALP) decrease have longer survival times than patients whose levels do not decrease. We compared survival times between patients with PSC treated with UDCA or placebo, with and without decreased levels of ALP.

Methods: We collected data from patients enrolled in the Scandinavian PSC UDCA trial. Patients were randomly assigned to groups given UDCA (17-23 mg/kg/day, n = 97) or placebo (n = 101) from 1996-2001 and were followed until 2010. End points were death, liver transplantation, or cholangiocarcinoma. They were considered to be biochemical responders if they had serum levels of ALP that were normal or reduced by ≥40% after 1 year in the trial (regardless of whether they received UDCA or placebo). Numbers of patients surviving until the study end point were compared by using the Kaplan-Meier method.

Results: There were no differences in survival at the end of the study between patients given UDCA or placebo (P = .774, log-rank); 26 patients in the UDCA group and 29 in the placebo group reached an end point. On the basis of ALP levels, there were 79 responders and 116 nonresponders overall. Of patients given UDCA, significantly more biochemical responders survived for 10 years than nonresponders (P = .03, log-rank). However, differences remained significant regardless of group assignment; overall, patients with reductions in ALP level survived longer than patients without reductions in ALP (P = .0001, log-rank).

Conclusions: There is no significant difference in long-term survival between patients with PSC given UDCA (17-23 mg/kg/day) or placebo for 5 years. However, patients who have reduced or normal levels of ALP have longer survival times, regardless of whether they receive UDCA or placebo.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkaline Phosphatase / blood*
  • Cholagogues and Choleretics / therapeutic use*
  • Cholangitis, Sclerosing / drug therapy
  • Cholangitis, Sclerosing / mortality*
  • Cholangitis, Sclerosing / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Prognosis
  • Survival Analysis
  • Ursodeoxycholic Acid / therapeutic use*

Substances

  • Cholagogues and Choleretics
  • Placebos
  • Ursodeoxycholic Acid
  • Alkaline Phosphatase