Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase
Year: 2020
Type: article
Abstract: INTRODUCTION: 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.
Authors: Carla F. Murillo Perez, Maren H. Harms, Keith D. Lindor, Henk R. van Buuren, Gideon M. Hirschfield, Christophe Corpechot, Adriaan J. van der Meer, Jordan J. Feld, Aliya Gulamhusein, Willem J. Lammers, Cyriel Y. Ponsioen, Marco Carbone, Andrew L. Mason, Marlyn J. Mayo, Pietro Invernizzi, Pier Maria Battezzati, Annarosa Floreani, Ana Lleo, Frederik Nevens, Kris V. Kowdley, Tony Bruns, George N. Dalekos, Nikolaos K. Gatselis, Douglas Thorburn, Palak J. Trivedi, Xavier Verhelst, Albert Parés, Harry L.A. Janssen, Bettina E. Hansen, on behalf of the GLOBAL PBC Study Group
Institutions: University Health Network, Toronto General Hospital, Erasmus MC, Arizona State University, Hôpital Saint-Antoine, Amsterdam UMC Location University of Amsterdam, University of Milano-Bicocca, University of Alberta, The University of Texas Southwestern Medical Center, University of Milan, University of Padua, Humanitas University, IRCCS Humanitas Research Hospital, KU Leuven, Swedish Medical Center, Universitätsklinikum Aachen, Jena University Hospital, Friedrich Schiller University Jena, RWTH Aachen University, University of Thessaly, The Royal Free Hospital, National Institute for Health and Care Research, University of Birmingham, Ghent University Hospital, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, University of Toronto
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Falk Foundation, Gilead Sciences, Arizona State University, University of Texas Southwestern Medical Center, Università degli Studi di Milano, Friedrich-Schiller-Universität Jena, Intercept Pharmaceuticals, University of Alberta, National Institute for Health and Care Research, Universitair Ziekenhuis Gent, Università degli Studi di Padova, Universiteit Gent, Astellas Pharma, Universitat de Barcelona, Humanitas University, University of Thessaly, Dr. Falk Pharma, Norgine, Novartis Pharma, Erasmus Universitair Medisch Centrum Rotterdam, Cilag
OpenAlex ID: W3007762014