OBJECTIVE: The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. BACKGROUND: Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. METHODS: We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. RESULTS: Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). CONCLUSIONS: Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts.
OBJECTIVE: The aim of this study was to determine the predictive value of machine perfusate analysis on graft outcome. BACKGROUND: Ex situ machine perfusion (MP) is gaining increasing interest to potentially repair injured organs and to assess organ function. In the field of liver transplantation, however, no studies exist on reliable prediction of graft function during MP. METHODS: We have used hypothermic oxygenated perfusion (HOPE) for donation after circulatory death (DCD) or extended criteria donation after brain death (DBD) human liver grafts during the last 7 years. Our series includes 100 HOPE-treated liver-transplanted patients with an overall tumor-censored 5-year graft survival of 89%. We monitored 54 livers during HOPE in terms of fluorometric analysis of released mitochondrial flavin (flavin mononucleotide, FMN) in the machine perfusate. RESULTS: Real-time optical measurement of mitochondrial FMN release in machine perfusates of livers disclosed a strong correlation with lactate clearance and coagulation factors at day 1 and 2 after transplantation. Receiver-operating characteristic curve analysis revealed an area under the curve (AUROC) of 0.79 [95% confidence interval (CI), 0.62-0.97] for severe allograft dysfunction and for early graft loss (AUROC 0.93, 95% CI, 0.84-1.0). CONCLUSIONS: Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts.
Authors: Carlo D L Ceresa; David Nasralla; Joerg-Matthias Pollok; Peter J Friend Journal: Nat Rev Gastroenterol Hepatol Date: 2022-01-07 Impact factor: 46.802
Authors: Riccardo De Carlis; Andrea Lauterio; Leonardo Centonze; Vincenzo Buscemi; Andrea Schlegel; Paolo Muiesan; Luciano De Carlis Journal: Updates Surg Date: 2022-02-28
Authors: Shannon N Tessier; Reinier J de Vries; Casie A Pendexter; Stephanie E J Cronin; Sinan Ozer; Ehab O A Hafiz; Siavash Raigani; Joao Paulo Oliveira-Costa; Benjamin T Wilks; Manuela Lopera Higuita; Thomas M van Gulik; Osman Berk Usta; Shannon L Stott; Heidi Yeh; Martin L Yarmush; Korkut Uygun; Mehmet Toner Journal: Nat Commun Date: 2022-07-15 Impact factor: 17.694
Authors: Isabel M A Brüggenwirth; Willemijn S van der Plas; Otto B van Leeuwen; Adam M Thorne; Michel Rayar; Vincent E de Meijer; Robert J Porte Journal: Artif Organs Date: 2021-12-16 Impact factor: 2.663