Evolving Trends in Machine Perfusion for Liver Transplantation

Dutkowski, P.; Guarrera, James V.; Jonge, Jeroen de; Martins, Paulo N.; Porte, Robert J.; Clavien, Pierre‐Alain

doi:10.1053/j.gastro.2018.12.037

Cited by 91 publications

(111 citation statements)

References 49 publications

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“…However, marginal grafts are particularly susceptible to I/R injury and may lead to early graft dysfunction and primary nonfunction. Organ perfusion support has recently been reported to be an effective procedure to overcome this issue, and a randomized trial demonstrated the efficacy of normothermic preservation using a perfusion machine to attenuate hepatic I/R injury . However, the cost and transportation of the machine are the major obstacles for the widespread use of this procedure.…”

Section: Discussionmentioning

confidence: 99%

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis

Yamada

Karasawa

Wakiya

et al. 2020

American Journal of Transplantation

157

101

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Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury. K E Y W O R D Scell death, liver transplantation/hepatology, liver transplantation: living donor, translational research/science

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Section: Discussionmentioning

confidence: 99%

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis

Yamada

Karasawa

Wakiya

et al. 2020

American Journal of Transplantation

157

101

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“…10 The underlying protective mechanism of NRP and all other perfusion techniques is therefore dependent on the amount of injury and on the concurrent response mechanisms during machine liver perfusion. 8 This discovery should lead in the future to concepts assessing and predicting graft quality during machine perfusion. 8,9 Fourth, the authors describe the period of postmortem NRP as economically favorable.…”

Section: Normothermic Regional Perfusion -What Is the Benefit?mentioning

confidence: 99%

“…6,7 Based on this, it is currently unclear if NRP can be expected to increase utilization of more livers grafts, which is one of the main targets of machine liver perfusion approaches. 8,9 Additionally, the number of declined livers prior to donor withdrawal of treatment and perfusion and, at what risk, is frequently underreported in recent available cohort studies. 1,6,7,9 For a more transparent comparison, all future studies on machine liver perfusion should therefore include a detailed report of parameters on graft quality, utilization rate and graft loss after transplantation ( Table 1).…”

Section: Normothermic Regional Perfusion -What Is the Benefit?mentioning

confidence: 99%

“…1,6,7,9 For a more transparent comparison, all future studies on machine liver perfusion should therefore include a detailed report of parameters on graft quality, utilization rate and graft loss after transplantation ( Table 1). 8 Third, the authors provide no information on the assessment of liver quality during NRP, which is of the utmost importance, when higher risk grafts are perfused. Currently available markers in use include liver enzymes and lactate or bile production, which were recently shown not to be sufficient to exclude liver graft failure in the recipient.…”

Section: Normothermic Regional Perfusion -What Is the Benefit?mentioning

confidence: 99%

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Normothermic regional perfusion – What is the benefit?

Schlegel

Muiesan

Dutkowski

2019

Journal of Hepatology

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“…Traditional endpoints of liver transplantation studies, such as early allograft dysfunction, may no longer apply with integration of machine perfusion. One of the diagnostic criteria for EAD involves assessment of hepatic enzyme injury markers, but critics argue that washout of these enzymes during NMP results in artificially lower posttransplant serum levels . As a result, trials with EAD or peak enzyme level as primary endpoints lack clinical relevance and there is a need to focus on patient and graft outcomes instead of traditional lab markers.…”

Section: Future Directions For Liver Perfusionmentioning

confidence: 99%

Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusion

et al. 2019

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Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusionRecent advances in machine perfusion technology have reinvigorated the field of liver transplantation with the possibilities of vastly improving the efficiency and safety of the life-saving procedure. With this improved preservation technology, transplant surgeons are now able to use previously untransplantable donor livers without significantly compromising patient outcomes. Early clinical studies demonstrate the ability to extend preservation times and assess a graft's potential viability using normothermic machine perfusion, in addition to restoring the energy supply in donor livers by supporting metabolism through circulation of vital nutrients and blood-based oxygen carriers. Future endeavors for surgeons and scientists should focus on improving criteria to assess viability, optimizing protocols for perfusion research, investigating mechanisms of poor graft viability, and targeting these mechanisms with novel therapies to improve graft function prior to transplantation. Long-term goals include extending preservation times on the scale of days to weeks, enabling long-distance organ sharing, and establishing regional organ perfusion centers to streamline the procurement, perfusion, and transplantation process.

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Evolving Trends in Machine Perfusion for Liver Transplantation

Cited by 91 publications

References 49 publications

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis

Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis

Normothermic regional perfusion – What is the benefit?

Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusion

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