{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:47:00Z","timestamp":1789001220520,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T00:00:00Z","timestamp":1522972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T00:00:00Z","timestamp":1522972800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44\u2010year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970\u20101979 (n = 143), 1980\u20101989 (n = 858), 1990\u20101999 (n = 1,754), 2000\u20102009 (n = 1,815), and \u22652010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2\u20103 years per decade from 46.9 \u00b1 10.1 years in the 1970s to 57.0 \u00b1 12.1 years from 2010 onward (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970\u20101989) to 76.5% (1990\u20102014) (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris\u2010I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001) and higher 10\u2010year transplant\u2010free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and\/or a changing environmental trigger. (H<jats:sc>epatology<\/jats:sc> 2018;67:1920\u20101930).<\/jats:p>","DOI":"10.1002\/hep.29717","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T01:56:24Z","timestamp":1512784584000},"page":"1920-1930","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":79,"title":["Milder disease stage in patients with primary biliary cholangitis over a 44\u2010year period: A changing natural history"],"prefix":"10.1097","volume":"67","author":[{"given":"Carla F.","family":"Murillo Perez","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital,University Health Network,Toronto,ON,Canada"},{"name":"Insitute of Medical Science,University of Toronto,Toronto,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-569X","authenticated-orcid":false,"given":"Jorn C.","family":"Goet","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology,Erasmus University Medical Center,Rotterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem J.","family":"Lammers","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology,Erasmus University Medical Center,Rotterdam,The Netherlands"}],"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,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk R.","family":"van Buuren","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology,Erasmus University Medical Center,Rotterdam,The Netherlands"}],"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"}]},{"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery,University of Milan\u2010Bicocca,Milan,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[{"name":"Divison of Gastroenterology and Hepatology,University of Alberta,Edmonton,AB,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Corpechot","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Inflammatoires des VoiesBiliaires,H\u00f4pital Saint\u2010Antoine,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery,University of Milan\u2010Bicocca,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,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"given":"Annarosa","family":"Floreani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Pares","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Cl\u00ednic, CIBERehd, IDIBAPS,University of Barcelona,Barcelona,Spain"}],"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 Care Network,Swedish Medical Center,Seattle,WA"}],"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 of Jena,Jena,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George N.","family":"Dalekos","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine,University of Thessaly,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"}]},{"given":"Gideon","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"NIHR, Biomedical Research Centre and Centre for Liver Research,University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas F.","family":"LaRusso","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Lindor","sequence":"additional","affiliation":[{"name":"Arizona State University,Phoenix,AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Zachou","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine,University of Thessaly,Larissa,Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Poupon","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Inflammatoires des VoiesBiliaires,H\u00f4pital Saint\u2010Antoine,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palak J.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"NIHR, Biomedical Research Centre and Centre for Liver Research,University of 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