The transportable oxygenated machine perfusion Airdrive ® , an innovative approach to safely expand the donor pool for liver transplantation

AbstractThe discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. Various strategies to cope with the donor shortage problem and to increase the use of suboptimal grafts have been explored. Machine perfusion has been applied ex situ to liver grafts in the effort to improve static cold-storage preservation. If a more extensive application of this technology confirms the preliminary results, machine perfusion will become crucial in increasing the donor pool as well as improving recipients' outcomes. In this review, the authors focused on the evolution of machine perfusion, from the first animal experiences to the latest evidence in humans, highlighting the pros and cons as well as the potential clinical applications of various types of machine.

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Ex vivo machine perfusion: current applications and future directions in liver transplantation

Langenbeck s Archives of Surgery ◽

10.1007/s00423-020-02014-7 ◽

2020 ◽

Author(s):

Julian Michelotto ◽

Joseph M. G. V. Gassner ◽

Simon Moosburner ◽

Vanessa Muth ◽

Madhukar S. Patel ◽

...

Keyword(s):

Liver Transplantation ◽

Ex Vivo ◽

Machine Perfusion ◽

Donor Organ ◽

Donor Pool ◽

Future Directions ◽

Link Type ◽

Expanded Criteria ◽

End Stage ◽

Liver Machine Perfusion

Abstract Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

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The Emerging Importance of Liver Sinusoidal Endothelial Cells in Regulating Injury during Machine Perfusion of Deceased Liver Donors

Seminars in Liver Disease ◽

10.1055/s-0038-1661371 ◽

2018 ◽

Vol 38 (03) ◽

pp. 252-259 ◽

Cited By ~ 1

Author(s):

Hynek Mergental ◽

Darius Mirza ◽

Simon Afford ◽

Ricky Bhogal

Keyword(s):

Liver Transplantation ◽

Deceased Donor ◽

Liver Sinusoidal Endothelial Cell ◽

Machine Perfusion ◽

Liver Transplants ◽

Liver Sinusoidal Endothelial Cells ◽

Donor Pool ◽

Donor Liver Transplantation ◽

Liver Donors

AbstractWhile majority of liver transplants worldwide continue to be performed using deceased donor organs, the demands for donor livers continues to exceed the current supply. In an attempt to maximize the number of potentially usable donor livers and expand the current donor pool, there is intense global research by various groups exploring the role of machine perfusion in the liver transplantation, particularly with respect to the machine perfusion of extended-criteria liver donors. In this review, the authors summarize the current field of machine perfusion strategies as applied to deceased donor liver transplantation and how therapeutic targeting of the liver sinusoidal endothelial cell may improve the quality of donor livers.

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Donation after Circulatory Death in Paediatric Liver Transplantation: Current Status and Future Perspectives in the Machine Perfusion Era

BioMed Research International ◽

10.1155/2018/1756069 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Roberta Angelico ◽

M. Thamara P. R. Perera ◽

Tommaso Maria Manzia ◽

Alessandro Parente ◽

Chiara Grimaldi ◽

...

Keyword(s):

Liver Transplantation ◽

Liver Perfusion ◽

Current Status ◽

Machine Perfusion ◽

Donation After Circulatory Death ◽

Future Perspectives ◽

Donor Pool ◽

Donor Support ◽

Paediatric Liver Transplantation ◽

Circulatory Death

Efforts have been made by the transplant community to expand the deceased donor pool in paediatric liver transplantation (LT). The growing experience on donation after circulatory death (DCD) for adult LT has encouraged its use also in children, albeit in selective cases, opening new perspectives for paediatric patients. Even though there has recently been a slight increase in the number of DCD livers transplanted in children, with satisfactory graft and patient outcomes, the use of DCD grafts in paediatric recipients is still controversial due to morbid outcomes associated with DCD grafts. In this context, recent advances in the optimization of donor support by extracorporeal membrane oxygenation and in the graft preservation by liver machine perfusion could find application in order to expand the donor pool in paediatric LT. In the present study we review the current literature on DCD liver grafts transplanted in children and on the use of extracorporeal donor support and liver perfusion machines in paediatrics, with the aim of defining the current status and future perspectives of paediatric LT.

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P0004 : The transportable machine perfusion airdrive®, A novel approach to safely expand the donor pool for liver transplantation

Journal of Hepatology ◽

10.1016/s0168-8278(15)30212-9 ◽

2015 ◽

Vol 62 ◽

pp. S292

Author(s):

P. Compagnon ◽

I. Ben Mosbah ◽

E. Levesque ◽

H. Hentati ◽

M. Disabato ◽

...

Keyword(s):

Liver Transplantation ◽

Machine Perfusion ◽

Donor Pool ◽

Novel Approach

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Rewarming Machine Perfusion System for Liver Transplantation

Journal of Medical Devices ◽

10.1115/1.4025189 ◽

2013 ◽

Vol 7 (4) ◽

Cited By ~ 4

Author(s):

Hiromichi Obara ◽

Naoto Matsuno ◽

Takanobu Shigeta ◽

Shin Enosawa ◽

Toshihiko Hirano ◽

...

Keyword(s):

Liver Transplantation ◽

Organ Donor ◽

Liver Graft ◽

Donation After Cardiac Death ◽

Organ Shortage ◽

Machine Perfusion ◽

Porcine Liver ◽

Donor Pool ◽

Liver Preservation ◽

End Stage

The liver is one of the most essential organs, and transplantation is an established treatment for patients with end-stage disease who have lost their liver function. However, organ shortage is a critical problem in transplantation; thus, the development of an innovative preservation system to adopt critical grafts obtained from extended criteria donors or donation after cardiac death donors as viable organs for transplantation is necessary. We recently developed a novel rewarming machine perfusion preservation system for liver transplantation, and herein discuss this system, which allows the perfusion temperature to be controlled during the transition from hypothermic to subnormothermic conditions. This system has two functions: (1) the preservation and recovery of organ function and (2) screening the organ for viability. To achieve these functions, this system has three features: (1) temperature control of the preservation perfusate and liver graft, (2) dual-controlled perfusion of the portal vein and hepatic artery, and (3) real-time monitoring of the perfusion conditions, including the flow rate, perfusion pressure and temperature. This system was useful for liver preservation and for evaluating the graft viability and recovery of functions during machine perfusion before transplantation. This novel rewarming machine preservation system was tested in an experimental model using porcine liver grafts. We report that this system has certain advantages in liver preservation, and believe that this system will positively contribute to the expansion of the organ donor pool.

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Mitochondrial Reprogramming—What Is the Benefit of Hypothermic Oxygenated Perfusion in Liver Transplantation?

Transplantology ◽

10.3390/transplantology2020015 ◽

2021 ◽

Vol 2 (2) ◽

pp. 149-161

Author(s):

Rebecca Panconesi ◽

Mauricio Flores Carvalho ◽

Matteo Mueller ◽

Philipp Dutkowski ◽

Paolo Muiesan ◽

...

Keyword(s):

Liver Transplantation ◽

Clinical Trials ◽

Randomized Controlled Trial ◽

Cohort Studies ◽

Controlled Trial ◽

Machine Perfusion ◽

Randomized Controlled ◽

Hypothermic Perfusion ◽

Underlying Mechanisms ◽

Circulatory Death

Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed.

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Ischemic postconditioning improves the outcome of organs from donors after cardiac death in a pig liver transplantation model and provides synergistic protection with hypothermic machine perfusion

Clinical Transplantation ◽

10.1111/ctr.14417 ◽

2021 ◽

Author(s):

Degong Jia ◽

Qi Pan ◽

Yijie Zhang ◽

Yang Yu ◽

Zhanyu Song ◽

...

Keyword(s):

Liver Transplantation ◽

Cardiac Death ◽

Ischemic Postconditioning ◽

Machine Perfusion ◽

Pig Liver ◽

Hypothermic Machine Perfusion ◽

Transplantation Model

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Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis

The American Surgeon ◽

10.1177/00031348211023427 ◽

2021 ◽

pp. 000313482110234

Author(s):

Angela Sickels ◽

Keyur B. Shah ◽

Brianna Ruch ◽

Adrian Cotterell ◽

Inna Tchoukina ◽

...

Keyword(s):

Liver Transplantation ◽

Total Artificial Heart ◽

Donor Pool ◽

Cardiac Rejection ◽

Recipient Age ◽

Hospital Stays ◽

The Mean ◽

Domino Liver Transplantation ◽

End Stage

Background Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients. Methods Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages. Results Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months. Discussion Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

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