Ex situ 86‐hour liver perfusion: Pushing the boundary of organ preservation

Liu, Qiang; Nassar, Ahmed; Buccini, Laura D.; Grady, Patrick; Soliman, Basem; Hassan, Ahmed; Pezzati, Daniele; Iuppa, Giuseppe; Uso, Teresa Diago; Miller, Charles M.; Quintini, Cristiano

doi:10.1002/lt.25007

Cited by 29 publications

(28 citation statements)

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“…In our preclinical work on porcine livers, we investigated the impact of different perfusates and temperature and found that the best outcomes were achieved when the organs were perfused as closely as possible to physiological conditions . We then reproduced our animal findings in a discarded human liver model using blood bank–obtained FFP and PRBCs, the closest perfusion solution to human whole blood. A potential advantage of such perfusate is the lack of white blood cells and platelets, which are cells that play a critical role in IRI …”

Section: Discussionmentioning

confidence: 79%

“…Clinical studies in ex situ preservation have employed packed red blood cells (PRBCs) as oxygen carriers in combination with a colloid extracellular solution (Gelofusine, B Braun, Melsungen, Germany), Steen solution (Gelofusine, B Braun), and 5% albumin). Fresh frozen plasma (FFP), the most physiological of all extracellular fluids, has never been tested in clinical NMP, while preclinical studies from our group and other researchers indicate that FFP may have an important role as a perfusion solution . Therefore, the primary aim of this exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of FFP in ex situ liver preservation.…”

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confidence: 99%

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Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma

et al. 2020

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The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation. Liver Transplantation 26 215-226 2020 AASLD.Among the strategies employed to improve liver allograft utilization, ex situ normothermic machine perfusion (NMP) preservation has drawn increasing interest in the last decade. The potential advantage of this technology over static cold storage is the ability to enhance preservation along with the capacity to assess and improve graft viability. This is of particular importance when considering organs from extended criteria donors. (1) The type of perfusion solution plays a critical role in the success of NMP. Clinical studies in ex situ preservation have employed packed red blood cells (PRBCs) as oxygen carriers in combination with a colloid extracellular solution (Gelofusine, B Braun, Melsungen, Germany), (2)(3)(4) Steen solution (Gelofusine, B Braun), (5) and 5% albumin (6)(7)(8) ). Fresh frozen plasma (FFP), the most physiological of all extracellular fluids, has never been tested liu et al.

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Section: Discussionmentioning

confidence: 79%

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confidence: 99%

Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma

et al. 2020

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“…[8][9][10] Extended preservation by HOPE, for example, could facilitate logistics for allocation and transplantation. As a proof-of-concept, a human discarded liver has been preserved for 86 h using ex situ NMP, 11 and an initially declined human liver has successfully been transplanted after preservation for 26 h, of which 17.5 h was SCS and 8.5 h was NMP. 12 However, few data are available regarding extended graft preservation by DHOPE, and, currently, the maximum reported preservation time using HOPE is 8 h. 10,13,14 We investigated the effects of extended preservation by applying end-ischemic DHOPE in a porcine liver ischemiareperfusion injury model.…”

Section: Introductionmentioning

confidence: 99%

Extended hypothermic oxygenated machine perfusion enables ex situ preservation of porcine livers for up to 24 hours

et al. 2020

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Static cold storage Extended hypotermic oxygenated machine perfusion enables ex situ preservation of porcine livers for up to 24 h Dynamic preservation with DHOPE Reperfusion and viability assessment 2 h SCS 2 h DHOPE 4 h reperfusion 2 h SCS 6 h DHOPE 4 h reperfusion 2 h SCS 24 h DHOPE 4 h reperfusion 8-11 h SCS 20 h DHOPE 3 h reperfusion 24 h SCS 4 h reperfusion Decreasing venous and arterial flows, no bile production, injured appearence Non-viable livers • Lactate clearance, blood pH, glucose, ALT • Biliary pH, bicarbonate, LDH • HMGB-1, IL-6, TNFα, cfDNA • Bile duct and liver parenchyma histology Viable livers, all with similar: Lactate <1.7 mmol/L, perfusate pH7.35-7.45, bile production >10 ml, biliary pH >7.45 Livers meet viability criteria during 2.5 h Highlights DHOPE can be extended for up to 24 h to prolong donor liver preservation time. Hepatocellular and biliary function is maintained after ex situ preservation by 24 h DHOPE. Extension of DHOPE for up to 24 h does not induce more injury compared to shorter preservation times. The initial results of extended preservation by DHOPE for discarded human livers are promising. Lay summary It has been suggested that preserving liver grafts with a technique called (dual) hypothermic oxygenated machine perfusion ([D]HOPE) leads to better outcomes after transplantation than if livers are stored on ice, especially if an organ is of lesser quality. In this study, we showed that DHOPE could be used to preserve liver grafts for up to 24 h. This extended procedure could be used globally to facilitate transplantation and expand the donor pool.

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“…9 Therapeutic potential An additional advantage of NMP is the opportunity to prolong the preservation period and to potentially apply repair strategies to improve graft quality. As proof-of-concept, a human discarded liver was preserved for 86 h using ex situ NMP, 10 and an initially declined human liver was successfully transplanted after preservation for 26 h, of which 8.5 h were with NMP. 11 Other potential therapeutic interventions include pharmacological defatting strategies, gene and (stem)cell therapy during NMP.…”

Section: Improved Preservationmentioning

confidence: 99%