Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase

Research output: Contribution to journalArticlepeer-review


  • Global PBC Study Group

Colleges, School and Institutes

External organisations

  • Erasmus University Medical Center
  • Centre de Re[Combining Acute Accent]fe[Combining Acute Accent]rence des Maladies Inflammatoires des VoiesBiliaires
  • Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre
  • Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
  • Alberta Glycomics Centre, University of Alberta, Alberta, Canada
  • Department of Health Sciences
  • Endocrinology Unit, Department of Medicine, University of Padua, Padua, Italy.
  • Humanitas University
  • University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium.
  • Liver Care Network
  • University Hospital RWTH Aachen, Germany. Electronic address: gkohls@ukaachen.de.
  • School of Physical Education and Sport Science, University of Thessaly, Trikala, Greece
  • The Sheila Sherlock Liver Centre
  • Ghent University Hospital, Ghent, Belgium.
  • ADEE Liaison University of Barcelona Barcelona Spain
  • The University of Toronto, Toronto, Canada


OBJECTIVES: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined.

METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated.

RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN.

DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.


Original languageEnglish
JournalThe American Journal of Gastroenterology
Early online date20 Feb 2020
Publication statusE-pub ahead of print - 20 Feb 2020