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dc.contributor.authorChurch, Rachel J
dc.contributor.authorKullak-Ublick, Gerd A
dc.contributor.authorAubrecht, Jiri
dc.contributor.authorBonkovsky, Herbert L
dc.contributor.authorChalasani, Naga
dc.contributor.authorFontana, Robert J
dc.contributor.authorGoepfert, Jens C
dc.contributor.authorHackman, Frances
dc.contributor.authorKing, Nicholas M P
dc.contributor.authorKirby, Simon
dc.contributor.authorKirby, Patrick
dc.contributor.authorMarcinak, John
dc.contributor.authorOrmarsdottir, Sif
dc.contributor.authorSchomaker, Shelli J
dc.contributor.authorSchuppe-Koistinen, Ina
dc.contributor.authorWolenski, Francis
dc.contributor.authorArber, Nadir
dc.contributor.authorMerz, Michael
dc.contributor.authorSauer, John-Michael
dc.contributor.authorAndrade, Raul J
dc.contributor.authorvan Bömmel, Florian
dc.contributor.authorPoynard, Thierry
dc.contributor.authorWatkins, Paul B
dc.date.accessioned2019-04-26T13:46:57Z
dc.date.available2019-04-26T13:46:57Z
dc.date.issued2019-02-01
dc.date.submitted2019-04
dc.identifier.citationCandidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort. 2019, 69(2):760-773 Hepatologyen_US
dc.identifier.issn1527-3350
dc.identifier.pmid29357190
dc.identifier.doi10.1002/hep.29802
dc.identifier.urihttp://hdl.handle.net/2336/620877
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractCurrent blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of 14 promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192 and n = 81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total cytokeratin 18 (K18), caspase cleaved K18, glutathione S-transferase α, alpha-fetoprotein, arginase-1, osteopontin (OPN), sorbitol dehydrogenase, fatty acid binding protein, cadherin-5, macrophage colony-stimulating factor receptor (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell-derived chemotaxin-2. Most candidate biomarkers were significantly altered in DILI cases compared with healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase than miR-122, and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplantation within 6 months of DILI onset. Prediction of prognosis among DILI patients using the Model for End-Stage Liver Disease was improved by incorporation of K18 and MCSFR levels. Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.en_US
dc.description.sponsorshipNational Institute of Diabetes and Digestive and Kidney Diseases Indiana University University of North Carolina University of Michigan Wake Forest University Innovative Medicines Initiative Joint Undertaking European Union's Seventh Framework Programme (FP7/2007-2013) National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals National Health Service Trust University of Nottinghamen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urlhttps://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.29802en_US
dc.subjectLifrarsjúkdómaren_US
dc.subjectLyfjamisnotkunen_US
dc.subject.meshBiomarkersen_US
dc.subject.meshChemical and Drug Induced Liver Injuryen_US
dc.titleCandidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.en_US
dc.typeArticleen_US
dc.contributor.department1 Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill, Research Triangle Park, NC. 2 Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC. 3 Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Switzerland. 4 Mechanistic Safety, Novartis Global Drug Development, Basel, Switzerland. 5 Drug Safety R&D, Pfizer Inc., Groton, CT. 6 Wake Forest University School of Medicine, Winston-Salem, NC. 7 School of Medicine, Indiana University, Indianapolis, IN. 8 University of Michigan, Ann Arbor, MI. 9 Natural and Medical Sciences Institute, Reutlingen, Germany. 10 Pfizer Inc, New York, NY. 11 Predictive Safety Testing Consortium, Tucson, AZ. 12 Takeda Pharmaceuticals, Deerfield, IL. 13 Global Patient Safety, AstraZeneca R&D, Gothenburg, Sweden. 14 Science for Life Laboratory, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. 15 Tel Aviv Sourasky Medical Center, Tel Aviv University, Israel. 16 Discovery and Investigative Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland. 17 Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain. 18 Section of Hepatology, Clinic of Gastroenterology and Hepatology, University Hospital Leipzig, Leipzig, Germany. 19 Department of Hepatology, Groupe Hospitalier Pitié Salpêtrière, University Pierre et Marie Curie, INSERM UMR 938, Paris, France.en_US
dc.identifier.journalHepatologyen_US
dc.rights.accessLandspitali Access - LSH-aðganguren_US
dc.departmentcodeGAS12
dc.source.journaltitleHepatology (Baltimore, Md.)


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