title: Graft-derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation.
abstract: Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients. Concentrations of MIF in the effluent were greater than those in the recipients' serum before and after reperfusion (58 [interquartile range, IQR:23-79] μg/mL vs 0.06 [IQR:0.03-0.07] μg/mL and 1.3 [IQR:0.7-1.8] μg/mL, respectively; both P<.001). Effluent MIF concentrations correlated with effluent concentrations of the cell injury markers ALT (R=.51, P<.01), AST (R=.51, P<.01), CK (R=.45, P=.01), and LDH (R=.56, P<.01). Patients who developed EAD had greater MIF concentrations in effluent and serum 10 minutes after reperfusion than patients without EAD (Effluent: 80 [IQR:63-118] μg/mL vs 36 [IQR:20-70] μg/mL, P=.02; Serum: 1.7 [IQR:1.2-2.5] μg/mL vs 1.1 [IQR:0.6-1.7] μg/mL, P<.001).
  
  
  
  Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Joanna
authors.identifier: 0000-0001-8081-3009
authors.initials: J
authors.lastname: Baron-Stefaniak
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Schiefer
authors.affiliation: Heart and Lung Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Plöchl
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Claus G
authors.initials: CG
authors.lastname: Krenn
authors.affiliation: Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Berlakovich
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: David M
authors.initials: DM
authors.lastname: Baron
authors.affiliation: Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Faybik
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: early allograft dysfunction; effluent; hepatic I/R injury; hepatocellular injury; liver transplantation; migration inhibitory factor