{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:27:24Z","timestamp":1791239244352,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014923","name":"CymaBay Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018262","name":"Intercept Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1\u2009year, are candidates for second\u2010line 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>UDCA\u2010treated 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 &lt;1.67\u2009\u00d7\u2009upper 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54\u2009years. The POISE criteria were met by 56.4% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05\u2009\u00d7\u2009ULN (0.82\u20131.33) vs. 2.37\u2009\u00d7\u2009ULN (1.72\u20133.69) at six months (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001). Of 235 patients with serum ALP &gt;1.9\u2009\u00d7\u2009ULN 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 &gt;1.9\u2009\u00d7\u2009ULN at six months and thus would have been identified early.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We can identify patients for second\u2010line therapy at six months using an ALP threshold of 1.9\u2009\u00d7\u2009ULN, given that approximately 90% of these patients are non\u2010responders according to POISE criteria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15592","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T02:59:38Z","timestamp":1683601178000},"page":"1497-1506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one\u2010year non\u2010responders and predicts survival"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7634-4537","authenticated-orcid":false,"given":"C. Fiorella","family":"Murillo\u00a0Perez","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Schiff Center for Liver Diseases, Division of Digestive Health and Liver Diseases University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Hassanally","sequence":"additional","affiliation":[{"name":"University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palak J.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Biomedical Research Centre and Centre for Liver Research University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Corpechot","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Inflammatoires des Voies Biliaires H\u00f4pital Saint\u2010Antoine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan J.","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J.","family":"Lammers","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1344-3452","authenticated-orcid":false,"given":"Pier Maria","family":"Battezzati","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-5621","authenticated-orcid":false,"given":"Keith D.","family":"Lindor","sequence":"additional","affiliation":[{"name":"Arizona State University  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Nevens","sequence":"additional","affiliation":[{"name":"Department of Hepatology University Hospitals Leuven, KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Institute Northwest  Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5576-6914","authenticated-orcid":false,"given":"Tony","family":"Bruns","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV Jena University Hospital, Friedrich Schiller University, Jena, Department of Internal Medicine III, University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Cazzagon","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarosa","family":"Floreani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology University of Padua  Padua Italy"},{"name":"IRCCS Negrar  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-9522","authenticated-orcid":false,"given":"Andrew L.","family":"Mason","sequence":"additional","affiliation":[{"name":"Divison of Gastroenterology and Hepatology University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya","family":"Gulamhusein","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyriel Y.","family":"Ponsioen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-0443","authenticated-orcid":false,"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery University of Milano\u2010Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-7902","authenticated-orcid":false,"given":"Ana","family":"Lleo","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Department of Biomedical Sciences Humanitas University  Rozzano (Milan) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlyn J.","family":"Mayo","sequence":"additional","affiliation":[{"name":"Digestive and Liver diseases UT Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-8464","authenticated-orcid":false,"given":"George N.","family":"Dalekos","sequence":"additional","affiliation":[{"name":"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\u2010LIVER) General University Hospital of Larissa  Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos K.","family":"Gatselis","sequence":"additional","affiliation":[{"name":"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\u2010LIVER) General University Hospital of Larissa  Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Thorburn","sequence":"additional","affiliation":[{"name":"The Sheila Sherlock Liver Centre The Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-5415","authenticated-orcid":false,"given":"Xavier","family":"Verhelst","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Par\u00e9s","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Cl\u00ednic de Barcelona, Health Care Provider of the European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) CIBERehd IDIBAPS, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-1586","authenticated-orcid":false,"given":"Maria\u2010Carlota","family":"Londo\u00f1o","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Cl\u00ednic de Barcelona, Health Care Provider of the European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) CIBERehd IDIBAPS, University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto Ontario Canada"},{"name":"Erasmus MC University Medical Center Rotterdam  Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-1998","authenticated-orcid":false,"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery University of Milano\u2010Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Vuppalanchi","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon 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to ursodeoxycholic acid may be assessed earlier to allow second\u2010line therapy in patients with unresponsive primary biliary cholangitis","author":"Can\u00e7ado GGL","year":"2022"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15533"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.12.005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.12.010"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32426"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T08:51:11Z","timestamp":1702025471000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/liv.15592"],"URL":"https:\/\/doi.org\/10.1111\/liv.15592","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]},"assertion":[{"value":"2023-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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