title: Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis.
abstract: Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. It has been recently proposed that an alkaline phosphatase (ALP) decline of more than 40% in baseline value or a normal level after 1 year of UDCA treatment (Barcelona criteria) could serve as a good marker of long-term prognosis. Our aim was to define the best efficient set of biochemistries able to identify UDCA-treated patients at risk of death or liver transplantation (LT). The efficiency of several combinations of serum bilirubin, ALP, and aspartate aminotransferase (AST) threshold values to predict outcome was assessed after 1 year of treatment in 292 patients with PBC. Patients showing ALP <3 upper limit of normal (ULN), AST <2 ULN, and bilirubin </=1 mg/dL after 1 year of UDCA had a 10-year transplant-free survival rate of 90% (95% confidence interval, 81%-95%), compared to 51% (95% confidence interval, 38%-64%) for those who did not (P < 0.001). Patients were less well discriminated by the Barcelona criteria (79% versus 63%). Independent predictive factors of death or LT were baseline serum bilirubin level >1 mg/dL (relative risk [RR], 1.7), histologic stage >/=3 (RR, 1.5), interface hepatitis (RR, 1.9), and the absence of biochemical response (ALP >3 ULN or AST >2 ULN, or bilirubin >1 mg/dL) (RR, 2.3). Antinuclear antibodies against gp210 or Sp100 proteins were associated with death or LT in univariate but not in multivariate analysis.
  
  
  CONCLUSIONS
  This study defines the best efficient biochemical response to UDCA, which, independent of baseline predictive factors, identifies patients with PBC with a good long-term prognosis. Patients who fail to achieve this response and those with interface hepatitis or advanced histological stage should be targeted for further therapeutic research.
authors.affiliation: Hepatology Department, Reference Center for Inflammatory Biliary Diseases, Saint-Antoine Hospital, National Institute of Health and Medical Research (INSERM), Pierre et Marie Curie University (Paris 6), France. christophe.corpechot@sat.aphp.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Corpechot
authors.forename: Ludovico
authors.initials: L
authors.lastname: Abenavoli
authors.forename: Nabila
authors.initials: N
authors.lastname: Rabahi
authors.forename: Yves
authors.initials: Y
authors.lastname: Chrétien
authors.forename: Tony
authors.initials: T
authors.lastname: Andréani
authors.forename: Catherine
authors.initials: C
authors.lastname: Johanet
authors.forename: Olivier
authors.initials: O
authors.lastname: Chazouillères
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon