{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:43:45Z","timestamp":1790383425768,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Queen Elizabeth Hospital Birmingham Charity\u2019s Liver Foundation UK","award":["RCDE20701"],"award-info":[{"award-number":["RCDE20701"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>\n                    Strategies to increase the use of steatotic donor livers are required to tackle the mortality on the transplant waiting list. We aimed to test the efficacy of pharmacological enhancement of the lipid metabolism of human livers during ex situ normothermic machine perfusion to promote defatting and improve the functional recovery of the organs. Because of steatosis, 10 livers were discarded and were allocated either to a defatting group that had the perfusate supplemented with a combination of drugs to enhance lipid metabolism or to a control group that received perfusion fluid with vehicle only. Steatosis was assessed using tissue homogenate and histological analyses. Markers for lipid oxidation and solubilization, oxidative injury, inflammation, and biliary function were evaluated by enzyme\u2010linked immunosorbent assay, immunohistochemistry, and in\u2010gel protein detection. Treatment reduced tissue triglycerides by 38% and macrovesicular steatosis by 40% over 6\u00a0hours. This effect was driven by increased solubility of the triglycerides (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.04), and mitochondrial oxidation as assessed by increased ketogenesis (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.008) and adenosine triphosphate synthesis (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.01) were associated with increased levels of the enzymes acyl\u2010coenzyme A oxidase 1, carnitine palmitoyltransferase 1A, and acetyl\u2010coenzyme A synthetase. Concomitantly, defatted livers exhibited enhanced metabolic functional parameters such as urea production (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.03), lower vascular resistance, lower release of alanine aminotransferase (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.049), and higher bile production (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.008) with a higher bile pH (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.03). The treatment down\u2010regulated the expression of markers for oxidative injury as well as activation of immune cells (CD14; CD11b) and reduced the release of inflammatory cytokines in the perfusate (tumor necrosis factor \u03b1; interleukin 1\u03b2). In conclusion, pharmacological enhancement of intracellular lipid metabolism during normothermic machine perfusion decreased the lipid content of human livers within 6\u00a0hours. It also improved the intracellular metabolic support to the organs, leading to successful functional recovery and decreased expression of markers of reperfusion injury.\n                  <\/jats:p>","DOI":"10.1002\/lt.25439","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T01:14:05Z","timestamp":1551402845000},"page":"1007-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Manipulation of Lipid Metabolism During Normothermic Machine Perfusion: Effect of Defatting Therapies on Donor Liver Functional Recovery"],"prefix":"10.1097","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1709-9284","authenticated-orcid":false,"given":"Yuri L.","family":"Boteon","sequence":"first","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Attard","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda P. C. S.","family":"Boteon","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Wallace","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Reynolds","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hubscher","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Department of Cellular Pathology,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius F.","family":"Mirza","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hynek","family":"Mergental","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky H.","family":"Bhogal","sequence":"additional","affiliation":[{"name":"The Royal Marsden, Department of Academic Surgery,Fulham Road,Chelsea,London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Afford","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham Biomedical Research Centre,University Hospitals Birmingham National Health Service Foundation Trust,Birmingham,United Kingdom"},{"name":"Centre for Liver and Gastrointestinal Research,Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"lt25439-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1053\/j.gastro.2007.03.055","article-title":"Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease","volume":"132","year":"2007","journal-title":"Gastroenterology"},{"key":"lt25439-bib-0002-20240115","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s11605-015-2832-1","article-title":"Donor hepatic steatosis and outcome after liver transplantation: a systematic review","volume":"19","year":"2015","journal-title":"J Gastrointest Surg"},{"key":"lt25439-bib-0003-20240115","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.3748\/wjg.v19.i29.4638","article-title":"Strategies to rescue steatotic livers before transplantation in clinical and experimental studies","volume":"19","year":"2013","journal-title":"World J Gastroenterol"},{"key":"lt25439-bib-0004-20240115","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s002689900479","article-title":"Hepatic steatosis in liver transplant donors: common feature of donor population?","volume":"22","year":"1998","journal-title":"World J Surg"},{"key":"lt25439-bib-0005-20240115","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/lt.24972","article-title":"Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion","volume":"24","year":"2018","journal-title":"Liver Transpl"},{"key":"lt25439-bib-0006-20240115","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ymben.2009.05.005","article-title":"Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo","volume":"11","year":"2009","journal-title":"Metab 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ONE"},{"key":"lt25439-bib-0011-20240115","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1111\/ajt.14992","article-title":"Ex situ machine perfusion as a tool to recondition steatotic donor livers: troublesome features of fatty livers and the role of defatting therapies. A systematic review","volume":"18","year":"2018","journal-title":"Am J Transplant"},{"key":"lt25439-bib-0012-20240115","doi-asserted-by":"crossref","first-page":"e017733","DOI":"10.1136\/bmjopen-2017-017733","article-title":"Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open\u2010label, non\u2010randomised, prospective, single\u2010arm trial","volume":"7","year":"2017","journal-title":"BMJ Open"},{"key":"lt25439-bib-0013-20240115","first-page":"187","article-title":"Comparing of IRS and Her2 as immunohistochemical scoring schemes in gastroenteropancreatic neuroendocrine tumors","volume":"5","year":"2012","journal-title":"Int J Clin Exp Pathol"},{"key":"lt25439-bib-0014-20240115","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/00007890-198905000-00034","article-title":"Primary nonfunction of hepatic allografts with preexisting fatty 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Hepatol"},{"key":"lt25439-bib-0026-20240115","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/lt.24094","article-title":"Urea production during normothermic machine perfusion: price of success?","volume":"21","year":"2015","journal-title":"Liver Transpl"},{"key":"lt25439-bib-0027-20240115","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/lt.24451","article-title":"Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers","volume":"22","year":"2016","journal-title":"Liver Transpl"}],"container-title":["Liver Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flt.25439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lt.25439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lt.25439","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01445473-201907000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T04:06:37Z","timestamp":1721016397000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01445473-201907000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1002\/lt.25439","relation":{},"ISSN":["1527-6465","1527-6473"],"issn-type":[{"value":"1527-6465","type":"print"},{"value":"1527-6473","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,20]]},"assertion":[{"value":"2018-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}