{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:11:19Z","timestamp":1793232679932,"version":"4.5.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005622","name":"Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Increased use of high\u2010risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell\u2013based fluid at 37\u00b0C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate\u2010clearing (LC) and non\u2010lactate\u2010clearing (non\u2010LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol\/L in the LC and non\u2010LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow &gt;150 and 500 mL\/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non\u2010LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non\u2010LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high\u2010risk livers.<\/jats:p>","DOI":"10.1002\/lt.25291","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T21:45:39Z","timestamp":1540503939000},"page":"1453-1469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High\u2010Risk Livers Using Normothermic Machine Perfusion"],"prefix":"10.1097","volume":"24","author":[{"given":"Hynek","family":"Mergental","sequence":"first","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"},{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnaby T. F.","family":"Stephenson","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Laing","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"},{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Kirkham","sequence":"additional","affiliation":[{"name":"Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Sciences,University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desley A. H.","family":"Neil","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine L.","family":"Wallace","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri L.","family":"Boteon","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"},{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-9550","authenticated-orcid":false,"given":"Jeannette","family":"Widmer","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky H.","family":"Bhogal","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"},{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Thamara P. R.","family":"Perera","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Smith","sequence":"additional","affiliation":[{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Yap","sequence":"additional","affiliation":[{"name":"Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Sciences,University of Birmingham,Birmingham,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan G.","family":"H\u00fcbscher","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius F.","family":"Mirza","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"},{"name":"Liver Unit,Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Afford","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Birmingham, Liver Biomedical Research Centre, College of Medical and Dental Sciences,University of Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"key":"lt25291-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1016\/S0140-6736(15)00680-7","article-title":"Implementation of the Lancet Standing Commission on Liver Disease in the UK","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"lt25291-bib-0003-20240115","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0140-6736(90)92195-N","article-title":"Eosinophilia\u2010myalgia syndrome associated with prescribed L\u2010tryptophan","volume":"336","year":"1990","journal-title":"Lancet"},{"key":"lt25291-bib-0004-20240115","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1097\/00007890-199304000-00024","article-title":"Risk factors for primary dysfunction after liver transplantation\u2013a multivariate 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transplantation","volume":"68","year":"2018","journal-title":"J Hepatol"},{"key":"lt25291-bib-0011-20240115","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1111\/ajt.13708","article-title":"Liver transplantation after ex vivo normothermic machine preservation: a phase 1 (first\u2010in\u2010man) clinical trial","volume":"16","year":"2016","journal-title":"Am J Transplant"},{"key":"lt25291-bib-0012-20240115","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1111\/ajt.13875","article-title":"Transplantation of declined liver allografts following normothermic ex\u2010situ evaluation","volume":"16","year":"2016","journal-title":"Am J Transplant"},{"key":"lt25291-bib-0013-20240115","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1111\/ajt.12374","article-title":"Normothermic machine perfusion of discarded liver grafts","volume":"13","year":"2013","journal-title":"Am J 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