Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one‐year non‐responders and predicts survival
Liver International, vol. 43, pp. 1497–1506
Abstract
BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response. METHODS: UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected. RESULTS: For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82-1.33) vs. 2.37 × ULN (1.72-3.69) at six months (p < .001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early. CONCLUSIONS: We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.
Authors 30
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Affiliation as printed
Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases University of Miami Miami Florida USA
Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA
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Affiliation as printed
University of Toronto Toronto Ontario Canada
University of Toronto, Toronto, Ontario, Canada
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National Institute for Health and Care Research · NIHR Birmingham Biomedical Research Centre · University of Birmingham
Affiliation as printed
National Institute for Health Research Birmingham Biomedical Research Centre and Centre for Liver Research University of Birmingham Birmingham UK
National Institute for Health Research Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
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Affiliation as printed
Centre de Référence des Maladies Inflammatoires des Voies Biliaires Hôpital Saint‐Antoine Paris France
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Affiliation as printed
Erasmus MC University Medical Center Rotterdam Rotterdam Netherlands
Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
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Affiliation as printed
Department of Health Sciences Università degli Studi di Milano Milan Italy
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Affiliation as printed
Arizona State University Phoenix Arizona USA
Arizona State University, Phoenix, Arizona, USA
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Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Hepatology University Hospitals Leuven, KU Leuven Leuven Belgium
Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
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Affiliation as printed
Liver Institute Northwest Washington USA
Liver Institute Northwest, Washington, USA
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Universitätsklinikum Aachen · Jena University Hospital · Friedrich Schiller University Jena · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine IV Jena University Hospital, Friedrich Schiller University, Jena, Department of Internal Medicine III, University Hospital RWTH Aachen Aachen Germany
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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Affiliation as printed
Department of Surgery, Oncology and Gastroenterology University of Padua Padua Italy
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Affiliation as printed
Department of Surgery, Oncology and Gastroenterology University of Padua Padua Italy
IRCCS Negrar Verona Italy
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
IRCCS Negrar, Verona, Italy
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Affiliation as printed
Divison of Gastroenterology and Hepatology University of Alberta Edmonton Alberta Canada
Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada
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University Health Network · Toronto General Hospital
Affiliation as printed
Toronto Centre for Liver Disease, Toronto General Hospital University Health Network Toronto Ontario Canada
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Amsterdam UMC Location University of Amsterdam
Affiliation as printed
Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam the Netherlands
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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Azienda Ospedaliera San Gerardo · University of Milano-Bicocca
Affiliation as printed
Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery University of Milano‐Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital Monza Italy
Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, Italy
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Humanitas University · IRCCS Humanitas Research Hospital
Affiliation as printed
Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Department of Biomedical Sciences Humanitas University Rozzano (Milan) Italy
Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Department of Biomedical Sciences, Humanitas University, Rozzano (Milan), Italy
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The University of Texas Southwestern Medical Center
Affiliation as printed
Digestive and Liver diseases UT Southwestern Medical Center Dallas Texas USA
Digestive and Liver diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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University Hospital of Larissa · General Hospital of Larisa, Greece
Affiliation as printed
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) General University Hospital of Larissa Larissa Greece
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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University Hospital of Larissa · General Hospital of Larisa, Greece
Affiliation as printed
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) General University Hospital of Larissa Larissa Greece
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, Full Member of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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Affiliation as printed
The Sheila Sherlock Liver Centre The Royal Free Hospital London UK
The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK
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Affiliation as printed
Department of Gastroenterology and Hepatology Ghent University Hospital Ghent Belgium
Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
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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
Affiliation as printed
Liver Unit, Hospital Clínic de Barcelona, Health Care Provider of the European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) CIBERehd IDIBAPS, University of Barcelona Barcelona Spain
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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
Affiliation as printed
Liver Unit, Hospital Clínic de Barcelona, Health Care Provider of the European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) CIBERehd IDIBAPS, University of Barcelona Barcelona Spain
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University Health Network · Toronto General Hospital · Erasmus MC
Affiliation as printed
Erasmus MC University Medical Center Rotterdam Rotterdam Netherlands
Toronto Centre for Liver Disease, Toronto General Hospital University Health Network Toronto Ontario Canada
Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Azienda Ospedaliera San Gerardo · University of Milano-Bicocca
Affiliation as printed
Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery University of Milano‐Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital Monza Italy
Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, Italy
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Indiana University School of Medicine
Affiliation as printed
Indiana University School of Medicine Indianapolis Indiana USA
Indiana University School of Medicine, Indianapolis, Indiana, USA
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University Health Network · Toronto General Hospital
Affiliation as printed
Toronto Centre for Liver Disease, Toronto General Hospital University Health Network Toronto Ontario Canada
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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University Health Network · University of Toronto · Toronto General Hospital · Erasmus MC
Affiliation as printed
Erasmus MC University Medical Center Rotterdam Rotterdam Netherlands
Toronto Centre for Liver Disease, Toronto General Hospital University Health Network Toronto Ontario Canada
University of Toronto Toronto Ontario Canada
Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
University of Toronto, Toronto, Ontario, Canada
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Cynthia Levy corresponding
Affiliation as printed
Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases University of Miami Miami Florida USA
Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA
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