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determinant of liver disease and mortality, but there is little evidence on noninvasive index for assessment of liver biological aging. We developed the Liver Aging Index (LAI) in the China Kadoorie Biobank (CKB,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200921,629) using Cox\u2010Gompertz proportional hazards model. The LAI incorporated three clinical factors (body mass index, systolic and diastolic blood pressure), eight plasma biomarkers (glucose, total cholesterol, triglycerides, high\u2010 and low\u2010density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and \u03b3\u2010glutamyl transpeptidase), and two imaging biomarkers (fat attenuation parameter and liver stiffness measurement). External validation was conducted in the National Health and Nutrition Examination Survey (NHANES;\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20093412) and the VCTE\u2010Prognosis cohort (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200912,170, 16 global centers). Across all cohorts, the LAI demonstrated strong discrimination for all\u2010cause mortality (AUROC: 0.764 in NHANES; 0.759 in VCTE\u2010Prognosis), outperforming chronological age (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Liver aging acceleration (LAA), defined as the difference between LAI and chronological age, was associated with substantially elevated risks: each 1\u2010SD increase in LAA conferred a 22%\u201385% higher risk of all\u2010cause mortality and a 34%\u2013170% higher risk of liver\u2010related event or mortality. Using genetic instruments identified in CKB, we found genetic predisposition to accelerated liver aging was associated with higher risks of cirrhosis and liver cancer (HR\u2009=\u20093.94 [3.20\u20134.86] and 7.82 [2.05\u201329.80]), further validated in Biobank Japan. Integrating genetics and proteomics revealed novel pathophysiological involvement of amyloid\u2010beta clearance pathway and amyloid precursor protein in liver aging. These findings demonstrate the feasibility of a noninvasive, liver\u2010specific biological aging index and provide new insights into mechanisms underlying liver aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70565","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T15:10:26Z","timestamp":1780240226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver\u2010Related Outcomes in Multicohorts"],"prefix":"10.1111","volume":"25","author":[{"given":"Zhiyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-8093","authenticated-orcid":false,"given":"Shanshan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Beijing Friendship Hospital Capital Medical University, State Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-0014","authenticated-orcid":false,"given":"Canqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"},{"name":"Center for Public Health and Epidemic Preparedness &amp; Response Peking University  Beijing China"},{"name":"Ministry of Education Key Laboratory of Epidemiology of Major Diseases (Peking University)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3651-6693","authenticated-orcid":false,"given":"Dianjianyi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"},{"name":"Center for Public Health and Epidemic Preparedness &amp; Response Peking University  Beijing China"},{"name":"Ministry of Education Key Laboratory of Epidemiology of Major Diseases (Peking University)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-6563","authenticated-orcid":false,"given":"Pei","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics, School of Public Health Peking University  Beijing China"},{"name":"Center for Public Health and Epidemic Preparedness &amp; Response Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5750-6588","authenticated-orcid":false,"given":"Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Trial Service Unit &amp; Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Trial Service Unit &amp; 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Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5530-1343","authenticated-orcid":false,"given":"Junshi","family":"Chen","sequence":"additional","affiliation":[{"name":"China National Center for Food Safety Risk Assessment  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9658-8050","authenticated-orcid":false,"given":"Seung Up","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0822-9673","authenticated-orcid":false,"given":"Salvatore","family":"Petta","sequence":"additional","affiliation":[{"name":"Sezione di Gastroenterologia, Di.Bi.M.I.S. University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Tsochatzis","sequence":"additional","affiliation":[{"name":"Royal Free Hospital University College London Institute for Liver and Digestive Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Boursier","sequence":"additional","affiliation":[{"name":"Hepato\u2010Gastroenterology and Digestive Oncology Department Angers University Hospital  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Bugianesi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Citt\u00e0 Della Salute e Della Scienza di Torino University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wah\u2010Kheong","family":"Chan","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8947","authenticated-orcid":false,"given":"Manuel","family":"Romero\u2010Gomez","sequence":"additional","affiliation":[{"name":"UCM Digestive Diseases, Virgen del Roc\u00edo University Hospital, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Institute of Biomedicine of Seville (IBiS) University of Seville  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Calleja","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Hospital Universitario Puerta de Hierro Majadahonda  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"de L\u00e9dinghen","sequence":"additional","affiliation":[{"name":"Echosens  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Cast\u00e9ra","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, UMR1149 (CRI), INSERM  Paris France"},{"name":"H\u00f4pital Beaujon, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Service D'h\u00e9patologie  Clichy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun J.","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-5299","authenticated-orcid":false,"given":"George Boon\u2010Bee","family":"Goh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Singapore General Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip Noel","family":"Newsome","sequence":"additional","affiliation":[{"name":"Institute of Hepatology, Faculty of Life Sciences &amp; 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