{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:21:58Z","timestamp":1790684518691,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007436","name":"Familjen Erling-Perssons Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007436","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2017,1]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>The occurrence of drug\u2010induced liver injury (DILI<\/jats:styled-content>) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI<\/jats:styled-content>, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI<\/jats:styled-content> cases and controls.<\/jats:p><\/jats:sec>Methods<\/jats:title>An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI<\/jats:styled-content> biomarker candidates generated a DILI<\/jats:styled-content> array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and\/or tuberculosis receiving treatment, DILI<\/jats:styled-content> cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins.<\/jats:p><\/jats:sec>Results<\/jats:title>We observed elevated levels of cadherin 5, type 2 (CDH<\/jats:styled-content>5) and fatty acid\u2010binding protein 1 (FABP<\/jats:styled-content>1) in DILI<\/jats:styled-content> cases. In the two longitudinal cohorts, CDH<\/jats:styled-content>5 was elevated already at baseline. FABP<\/jats:styled-content>1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT<\/jats:styled-content>). The elevations were verified in the DILI<\/jats:styled-content> cases treated with various drugs. In the heparin cohort, CDH<\/jats:styled-content>5 was stable over time whereas FABP<\/jats:styled-content>1 was elevated.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These results suggest that CDH<\/jats:styled-content>5 may have value as a susceptibility marker for DILI<\/jats:styled-content>. FABP<\/jats:styled-content>1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT<\/jats:styled-content> but likely with limited predictive value for the development of severe DILI<\/jats:styled-content>. Further studies are needed to determine the clinical utility of the proposed markers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13174","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T22:22:25Z","timestamp":1464214945000},"page":"132-140","source":"Crossref","is-referenced-by-count":34,"title":["Elevated levels of circulating CDH5 and FABP1 in association with human drug\u2010induced liver injury"],"prefix":"10.1111","volume":"37","author":[{"given":"Maria","family":"Mikus","sequence":"first","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Drobin","sequence":"additional","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Gry","sequence":"additional","affiliation":[{"name":"Global Safety Assessment Molecular Toxicology Former AstraZeneca R&D S\u00f6dert\u00e4lje Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Global Safety Assessment Molecular Toxicology Former AstraZeneca R&D S\u00f6dert\u00e4lje Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getnet","family":"Yimer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Aklillu","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyasu","family":"Makonnen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getachew","family":"Aderaye","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Roach","sequence":"additional","affiliation":[{"name":"Momenta Pharmaceuticals Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Fier","sequence":"additional","affiliation":[{"name":"Momenta Pharmaceuticals Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kampf","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology SciLifeLab Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"G\u00f6pfert","sequence":"additional","affiliation":[{"name":"Biochemistry Department Natural and Medical Sciences Institute at the University of Tuebingen Reutlingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Perazzo","sequence":"additional","affiliation":[{"name":"Hepatology Department H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Poynard","sequence":"additional","affiliation":[{"name":"Hepatology Department H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Stephens","sequence":"additional","affiliation":[{"name":"UGC Gastroenterologia y Hepatologia y Serv Farmacolog\u00eda Cl\u00ednica IBIMA, Hospital U Virgen de la Victoria University of Malaga M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal J.","family":"Andrade","sequence":"additional","affiliation":[{"name":"UGC Gastroenterologia y Hepatologia y Serv Farmacolog\u00eda Cl\u00ednica IBIMA, Hospital U Virgen de la Victoria University of Malaga M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Isabel","family":"Lucena","sequence":"additional","affiliation":[{"name":"UGC Gastroenterologia y Hepatologia y Serv Farmacolog\u00eda Cl\u00ednica IBIMA, Hospital U Virgen de la Victoria University of Malaga M\u00e1laga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Arber","sequence":"additional","affiliation":[{"name":"The Integrated Cancer Prevention Center Tel Aviv Sourasky Medical Center Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Uhl\u00e9n","sequence":"additional","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Schools of Medicine University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen M.","family":"Schwenk","sequence":"additional","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Affinity proteomics SciLifeLab School of Biotechnology KTH\u2010Royal Institute of Technology Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Schuppe\u2010Koistinen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden"},{"name":"AstraZeneca R&D Innovative Medicines Personalised Healthcare & Biomarkers SciLifeLab Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1750"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021844"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.58"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052270"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.34857"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22633"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004038"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr500609e"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.04.011"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.07.006"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1694"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.68.1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/147323001003800433"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33336"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.09.003"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.6.1589"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(03)00096-1"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080644"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2242"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12375"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/48.11.2055"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2012.11.007"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.11.024"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.02.011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2004.05.001"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-007-9182-4"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.1106"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.11.021"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13174","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13174","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.13174","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T17:29:31Z","timestamp":1696181371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.13174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,22]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/liv.13174"],"URL":"https:\/\/doi.org\/10.1111\/liv.13174","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,22]]}}}