{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:54:28Z","timestamp":1762145668133,"version":"3.40.5"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point\u2010of\u2010care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5\u00a0minutes (DCD\u20105min, n\u00a0=\u00a04) or 45\u00a0minutes (DCD\u201045min, n\u00a0=\u00a04) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow\u2010controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8\u00a0hours for analysis. DCD\u201045min livers had greater terminal portal vein pressure (8.5 vs. 13.3\u00a0mm Hg, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.005). During perfusion, DCD\u201045min livers had equivalent terminal lactate clearance (93% vs. 96%, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.344), greater terminal alanine aminotransferase (163 vs. 883\u00a0U\/L, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7\u00a0U\/L, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.002). DCD\u201045min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250\u00a0ng\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.029; and 158 vs. 293\u00a0ng\/mL, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.003; respectively). DCD\u20105min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD\u201045min livers did not. On blinded histologic evaluation, DCD\u201045min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP.<\/jats:p>","DOI":"10.1002\/hep4.1734","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T13:00:51Z","timestamp":1620133251000},"page":"1527-1542","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Point\u2010of\u2010Care Assessment of DCD Livers During Normothermic Machine Perfusion in a Nonhuman Primate Model"],"prefix":"10.1097","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1891-5412","authenticated-orcid":false,"given":"Samuel J.","family":"Kesseli","sequence":"first","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared N.","family":"Gloria","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-5642","authenticated-orcid":false,"given":"Nader","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7316-1989","authenticated-orcid":false,"given":"Samantha E.","family":"Halpern","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greta N.","family":"Cywinska","sequence":"additional","affiliation":[{"name":"Duke University,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-0699","authenticated-orcid":false,"given":"Dimitrios","family":"Moris","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2317-6549","authenticated-orcid":false,"given":"Brian I.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary W.","family":"Fitch","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-751X","authenticated-orcid":false,"given":"Cynthia D.","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Pathology,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathew G","family":"Hartwig","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical Center,Durham,NC,USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-385X","authenticated-orcid":false,"given":"Stuart","family":"Knechtle","sequence":"additional","affiliation":[{"name":"Department of Surgery,Duke University Medical 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