Rewarming Machine Perfusion System for Liver Transplantation

2013 ◽  
Vol 7 (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.

scholarly journals Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review

2020 ◽  
Vol 9 (4) ◽  
pp. 1046 ◽  
Author(s):  
Fungai Dengu ◽  
Syed Hussain Abbas ◽  
Georg Ebeling ◽  
David Nasralla
Keyword(s):  
Ex Vivo ◽  
Organ Donor ◽  
Therapeutic Interventions ◽  
Machine Perfusion ◽  
Real Potential ◽  
Ischaemia Reperfusion Injury ◽  
Donor Pool ◽  
Liver Preservation ◽  
Ischaemia Reperfusion ◽  
Normothermic Machine Perfusion

Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.

Disadvantage of Small (<60 kg) Adult Candidates on the Liver Transplantation Waitlist

2020 ◽  
Vol 30 (4) ◽  
pp. 349-354
Author(s):  
Anne-Baue R. M. van Dijk ◽  
Dimitri Sneiders ◽  
Sarwa Darwish Murad ◽  
Wojciech G. Polak ◽  
Hermien Hartog
Keyword(s):  
Liver Transplantation ◽  
Cox Regression ◽  
Adult Patients ◽  
Blood Type ◽  
Liver Graft ◽  
Donation After Cardiac Death ◽  
Type Model ◽  
Death Time ◽  
Matched Case ◽  
End Stage

Background: Small adult patients with lower bodyweight wait-listed for liver transplantation may face a shortage of size-matched whole-liver grafts. The objective of this study is to compare time to transplantation in adult patients with a bodyweight of <60 kg to patients with bodyweight ≥60 kg. Methods: A matched case–control study was conducted. Patients aged 18 years and older listed for liver transplantation at our transplant center, from 2007 to 2016 with a bodyweight <60 kg were manually matched 1:2 to control patients ≥ 60 kg. Matching was performed based on ABO blood type, model for end-stage liver disease score, (non)-standard exception status, and eligibility for donation after cardiac death. Time to transplantation was assessed with univariable Cox-regression. Results: In total, 23 cases with a bodyweight < 60 kg were matched to 46 average-sized control patients. Small adults were significantly disadvantaged for receiving a liver transplantation as compared to their average-sized counterpart (hazard ratio 0.47; 95% confidence interval 0.29-0.75, P = .002). At the end of follow-up, 14/23 (60.9%) of cases versus 35/46 of controls (76.1%) had received a liver transplantation. Conclusion: Small adults with a bodyweight below 60 kg are disadvantaged on the waitlist for a size-matched whole liver graft.

scholarly journals Machine Perfusion in Liver Transplantation: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-12
Author(s):  
Matas Jakubauskas ◽  
Lina Jakubauskiene ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Transplantation ◽  
Meta Analysis ◽  
Biliary Complication ◽  
Liver Graft ◽  
Machine Perfusion ◽  
Biliary Strictures ◽  
Normothermic Machine Perfusion ◽  
Organ Quality ◽  
End Stage

<b><i>Background:</i></b> Liver transplantation (LTx) is the only treatment option for patients with end-stage liver disease. Novel organ preservation techniques such as hypothermic machine perfusion (HMP) or normothermic machine perfusion (NMP) are under investigation in order to improve organ quality from extended criteria donors and donors after circulatory death. The aim of this study was to systematically review the literature reporting LTx outcomes using NMP or HMP compared to static cold storage (SCS). <b><i>Methods:</i></b> The following data were retrieved: graft primary nonfunction rate, early allograft dysfunction (EAD) rate, biliary complication rate, and 12-month graft and patient survival. A total of 15 studies were included (6 NMP and 9 HMP studies), and meta-analysis was performed only for HMP studies because NMP had considerable differences. <b><i>Results:</i></b> The systematic review showed the potential of NMP to reduce graft injury and lower the liver graft discard rate. The performed quantitative analyses showed that the use of HMP reduces the rate of EAD (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.34–0.76; <i>p</i> = 0.001; <i>I</i><sup>2</sup> = 0%) and non-anastomotic biliary strictures (OR 0.34; 95% CI 0.17–0.67; <i>p</i> = 0.002; <i>I</i><sup>2</sup> = 0%) compared to SCS. <b><i>Conclusion:</i></b> Our systematic review and meta-analysis revealed that the use of HMP reduces the rate of EAD and non-anastomotic biliary strictures compared to SCS.

Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System

2021 ◽  
Author(s):  
Rebecca Pinnelas ◽  
Jon A Kobashigawa
Keyword(s):  
Viral Vector ◽  
Ex Vivo ◽  
Donation After Cardiac Death ◽  
Machine Perfusion ◽  
Donor Pool ◽  
Complex Anatomy ◽  
Normothermic Perfusion ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Care System

Cardiac transplantation is the gold standard for treatment for select patients with end-stage heart failure, yet donor supply is limited. Ex vivo machine perfusion is an emerging technology capable of safely preserving organs and expanding the viable donor pool. The TransMedics® Organ Care System™ is an investigational device which mimics physiologic conditions while maintaining the heart in a warm, beating state rather than cold storage. The use of Organ Care System allows increased opportunities for using organs from marginal donors, distant procurement sites, donation after cardiac death, and in recipients with complex anatomy. In the future, bioengineering technologies including use of mesenchymal stem cells, viral vector delivery of gene therapy, and alternate devices may further broaden the field of ex vivo machine perfusion.

scholarly journals An Update on Usage of High-Risk Donors in Liver Transplantation

2021 ◽  
Vol 11 (1) ◽  
pp. 215
Author(s):  
Haris Muhammad ◽  
Duha Zaffar ◽  
Aniqa Tehreem ◽  
Peng-Sheng Ting ◽  
Cem Simsek ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Steady Increase ◽  
Organ Shortage ◽  
Donor Pool ◽  
End Stage Liver Disease ◽  
Split Liver ◽  
End Stage ◽  
Marginal Donors ◽  
Waitlist Mortality ◽  
The Ideal

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

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

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.

scholarly journals Organ transplantation and chronic disturbances in the health condition of the population – challenges and perspectives

2020 ◽  
Vol 5 (4) ◽  
pp. 82-88
Author(s):  
Arzu Kader Harmanci Seren ◽  
Keyword(s):  
Health Care Professionals ◽  
Medical Technology ◽  
Health Resources ◽  
Organ Donor ◽  
Chronic Kidney Failure ◽  
Health Condition ◽  
Organ Shortage ◽  
Donor Pool ◽  
Organ Failures ◽  
End Stage

End-stage organ failure cases are increasing around the World. Especially chronic kidney failure has been becoming a worldwide epidemic. Although available medical technology and human health resources capacity is enough to transplant organs and tissues to patients diagnosed with end-stage organ fail-ure, many people cannot access the transplantation services because of eco-nomic reasons and organ shortage. Thus, health care professionals should fo-cus on preventing chronic organ failures besides increasing the organ donor pool.

Immune Checkpoint Inhibitors in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Case Report and Literature Review

2020 ◽  
Vol 20 (9) ◽  
pp. 720-727
Author(s):  
Jianguo Qiu ◽  
Wei Tang ◽  
Chengyou Du
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Immune Checkpoint ◽  
Graft Rejection ◽  
Checkpoint Inhibitors ◽  
Liver Graft ◽  
Immune Checkpoints ◽  
Term Survival ◽  
Liver Preservation ◽  
Programmed Death

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied. Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT. Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed. Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival. Conclusions: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.

Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis

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.

Liver Transplantation for the Gastroenterologist

2015 ◽  
Author(s):  
Andreea M. Catana ◽  
Michael P. Curry
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Procurement ◽  
The United States ◽  
Waiting Lists ◽  
Liver Graft ◽  
Term Survival ◽  
End Stage Liver Disease ◽  
End Stage

The first liver transplantation (LT) was performed in 1963, and currently more than 65,000 people in the United States are living with a transplanted liver. In 2012, the number of adults who registered on the LT waiting list decreased for the first time since 2002; 10,143 candidates were added compared with 10,359 in 2011. LT offers long-term survival for complications of end-stage liver disease and prolongs life in properly selected patients, but problems such as donor deficit, geographic disparities, and long waiting lists remain. This overview of LT for the gastroenterologist details the indications for LT and patient selection, evaluation, liver organ allocation, prioritization for transplantation, transplantation benefit by the Model for End-Stage Liver Disease (MELD), MELD limitations, sources of liver graft, strategies employed to decrease the donor deficit, complications, and outcomes. Figures include indications for LT in Europe and the United States, Organ Procurement and Transplantation Network regions in the United States, the number of transplants and size of active waiting lists, mortality by MELD, regional disparity, patient survival rates with and without hepatitis C virus, and unadjusted patient and graft survival. Tables list LT milestones, indications for LT, contraindications for LT, minimal listing criteria for LT, criteria for LT in acute liver failure, LT evaluation process, adult recipient listing status 1A, and early posttransplantation complications. This review contains 7 highly rendered figures, 8 tables, and 46 references. 

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