{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:03:01Z","timestamp":1791597781976,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011033","name":"Thermo Fisher Scientific","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016120","name":"Departamento de Salud, Gobierno de Navarra","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016120","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020027","name":"Dr. Rolf M. Schwiete Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary sclerosing cholangitis (PSC) is a chronic liver disease characterised by inflammation and fibrosis of the bile ducts, conferring an increased risk of cholangiocarcinoma (CCA). However, detecting CCA early in PSC patients remains challenging due to the limited sensitivity of conventional diagnostic methods, including imaging or bile duct brush cytology during endoscopic retrograde cholangiopancreatography (ERCP). This study aims to evaluate the potential of bile cell\u2010free DNA (cfDNA) mutational analysis, termed the Bilemut assay, as a tool for CCA detection in PSC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty\u2010three PSC patients undergoing ERCP due to biliary strictures were prospectively recruited. Bile samples were collected, and cfDNA was extracted and analysed using the Oncomine Pan\u2010Cancer Cell\u2010Free assay. Twenty healthy liver donors were included for comparison. Samples with a mutant allele frequency (MAF) \u2265\u20090.1% were considered positive. Correlations between mutational status and clinical characteristics were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      cfDNA mutational analysis was successful in all bile samples. Mutations predominantly in\n                      <jats:italic>KRAS<\/jats:italic>\n                      ,\n                      <jats:italic>GNAS<\/jats:italic>\n                      , and\n                      <jats:italic>TP53<\/jats:italic>\n                      were detected in 36.5% (23\/63) of PSC patients, compared to 10% (2\/20) of healthy donors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0269). The clinical characteristics of Bilemut\u2010positive and \u2010negative patients were comparable, though there was a trend towards a lower prevalence of inflammatory bowel disease in the Bilemut\u2010positive group. Among PSC patients diagnosed with CCA during follow\u2010up, 75% were Bilemut\u2010positive, suggesting an association between mutational status and malignancy risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mutational analysis of cfDNA obtained from bile collected from PSC patients undergoing ERCP is feasible. Implementing the Bilemut assay may help identify patients needing closer surveillance and further imaging studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70049","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:55:02Z","timestamp":1741049702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mutational Analysis of Bile Cell\u2010Free DNA in Primary Sclerosing Cholangitis: A Pilot Study"],"prefix":"10.1111","volume":"45","author":[{"given":"Maria","family":"Arechederra","sequence":"first","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN University of Navarra  Pamplona Spain"},{"name":"IdiSNA Navarra Institute for Health Research  Pamplona Spain"},{"name":"National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-3097","authenticated-orcid":false,"given":"Emil","family":"Bik","sequence":"additional","affiliation":[{"name":"Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rojo","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-7125","authenticated-orcid":false,"given":"Jasmin","family":"Elurbide","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN University of Navarra  Pamplona Spain"},{"name":"National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Elizalde","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kruk","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Krasnod\u0119bski","sequence":"additional","affiliation":[{"name":"Department of General Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Pertkiewicz","sequence":"additional","affiliation":[{"name":"Department of General Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u0142awomir","family":"Kozie\u0142","sequence":"additional","affiliation":[{"name":"Department of General Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Gr\u0105t","sequence":"additional","affiliation":[{"name":"Department of General Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Raszeja\u2010Wyszomirska","sequence":"additional","affiliation":[{"name":"Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rullan","sequence":"additional","affiliation":[{"name":"IdiSNA Navarra Institute for Health Research  Pamplona Spain"},{"name":"Department of Gastroenterology and Hepatology Navarra University Hospital  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka","family":"Alkorta\u2010Aranburu","sequence":"additional","affiliation":[{"name":"CIMA LAB Diagnostics University of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Oy\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Hospital General Universitario Gregorio Mara\u00f1\u00f3n  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite G.","family":"Fern\u00e1ndez\u2010Barrena","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN University of Navarra  Pamplona Spain"},{"name":"IdiSNA Navarra Institute for Health Research  Pamplona Spain"},{"name":"National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena S.","family":"Candels","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER)  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Bia\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Pomeranian Medical University  Szczecin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Krupa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology With Internal Disease Unit Teaching Hospital No 1 in Rzesz\u00f3w  Rzesz\u00f3w Poland"},{"name":"Medical Department University of Rzesz\u00f3w  Rzesz\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai M.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t (TU)  Dresden Germany"},{"name":"Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t (TU)  Dresden Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, TUD Dresden University of Technology  Dresden Germany"},{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Urman","sequence":"additional","affiliation":[{"name":"IdiSNA Navarra Institute for Health Research  Pamplona Spain"},{"name":"Department of Gastroenterology and Hepatology Navarra University Hospital  Pamplona 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