학술논문
Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival.
Document Type
Academic Journal
Author
Murillo Perez CF; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Ioannou S; Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA.; Hassanally I; University of Toronto, Toronto, Ontario, Canada.; Trivedi PJ; National Institute for Health Research Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK.; Corpechot C; Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, Paris, France.; van der Meer AJ; Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.; Lammers WJ; Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.; Battezzati PM; Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.; Lindor KD; Arizona State University, Phoenix, Arizona, USA.; Nevens F; Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.; Kowdley KV; Liver Institute Northwest, Washington, USA.; Bruns T; Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.; Cazzagon N; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.; Floreani A; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.; IRCCS Negrar, Verona, Italy.; Mason AL; Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada.; Gulamhusein A; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Ponsioen CY; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.; Carbone M; 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.; Lleo A; Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Department of Biomedical Sciences, Humanitas University, Rozzano (Milan), Italy.; Mayo MJ; Digestive and Liver diseases, UT Southwestern Medical Center, Dallas, Texas, USA.; Dalekos GN; 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.; Gatselis NK; 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.; Thorburn D; The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK.; Verhelst X; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.; Parés A; 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.; Londoño MC; 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.; Janssen HLA; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.; Invernizzi P; 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.; Vuppalanchi R; Indiana University School of Medicine, Indianapolis, Indiana, USA.; Hirschfield GM; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; Hansen BE; 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.; Levy C; Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida, USA.
Source
Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE
Subject
Language
English
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.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)