{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:55:34Z","timestamp":1781812534252,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Cellular senescence is a hallmark of several liver diseases, including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Senescent cholangiocytes exhibit a senescence\u2010associated secretory phenotype (SASP), characterized by profibroinflammatory mediator release. Current cost\u2010effective biomarkers predicting disease progression, particularly for PSC, are limited and often lack mechanistic relevance. We sought to define a plasma biomarker signature for PSC and PBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma from early\u2010 and late\u2010stage PSC and PBC, alcoholic liver disease (ALD), inflammatory bowel disease (IBD) patients, and healthy controls was analyzed. Seventy\u2010one analytes were quantified using Luminex Multiplex Immunoassay or enzyme\u2010linked immunosorbent assay (ELISA). Principal component analysis (PCA) identified key patterns. Findings from the PSC cohort were then applied to additional cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Second principal component (PC2) (17 analytes, 17.1% variability) best separated PSC from controls. ANOVA showed significant differences in PC2 between early PSC vs. controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001), late PSC vs. controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and early vs. late PSC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). PC2 analytes also distinguished early PBC vs. controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0332), late PBC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and ALD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and early vs. late PBC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), but not IBD vs. controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.119). Logistic regression using PC2 demonstrated strong discrimination of early\u2010 and late\u2010stage PSC (AUC\u2009=\u20090.86) and control vs. early\u2010stage PSC (AUC\u2009=\u20090.83).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to define a plasma SASP biomarker signature associated with cholestatic liver disease. These analytes track disease stage and represent both mechanistic indicators and potential clinical trial endpoints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70279","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:02:03Z","timestamp":1771048923000},"page":"1065-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Biomarkers of Senescence in Cholestatic Liver Disease: A Signature of Risk Stratification and Progression"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-5450","authenticated-orcid":false,"given":"Steven\u00a0P.","family":"O'Hara","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela\u00a0Tietz","family":"Bogert","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Indiana University School of Public Health  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Indiana University School of Public Health  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0B.","family":"Allison","sequence":"additional","affiliation":[{"name":"Indiana University School of Public Health  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jair\u00a0Machado\u00a0Espindola","family":"Netto","sequence":"additional","affiliation":[{"name":"Department of Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James\u00a0L.","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Tchkonia","sequence":"additional","affiliation":[{"name":"Center for Advanced Gerotherapeutics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humza\u00a0M.","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Morgenthaler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad\u00a0H.","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Gastroenterology and Hepatology University of Missouri School of Medicine  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos\u00a0N.","family":"Lazaridis","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory\u00a0J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"LaRusso","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1506330"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26565"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.02.038"},{"key":"e_1_2_9_5_1","first-page":"10","article-title":"Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics","volume":"10","author":"Park J. 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