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BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

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Heart transplantation is the primary therapeutic option for patients with end-stage heart failure. The shortage of donors has been the main limiting factor for the increasing quantity of heart transplantation. With persistent updating and introduction of novel technologies, the donor pool has been increasingly expanded, such as using the heart from older donors, donors infected with hepatitis C virus, donors dying from drug overdose or donation after cardiac death (DCD) donors, etc. Meantime, the proportion of recipients with advanced age, multiple organ dysfunction, mechanical circulatory support and human leukocyte antigen antibody sensitization has been significantly increased in recent years. The shortage of donors, complication of recipients' conditions, individualized management of immunosuppressive therapy and prevention and treatment of long-term cardiac allograft vasculopathy are all challenges in the field of heart transplantation. In this article, novel progresses on donor pool expansion, improving the quality of recipients, strengthening the diagnosis and treatment of rejection, and preventing cardiac allograft vasculopathy were reviewed, aiming to prolong the survival and enhance the quality of life of patients with end-stage heart failure on the waiting list or underwent heart transplantation.

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Thoracic organ transplantation, including lung, heart, and heart-lung transplants are highly regarded as gold standard treatments for patients suffering from heart failure or chronic end stage lung conditions. The relatively high prevalence of conditions necessitating thoracic organ transplants combined with the lack of available organs has resulted in many either dying or becoming too ill to receive a transplant while on the waiting list. There is a dire need to increase both the number of organs available and the utilization of such organs. Improved preservation techniques beyond static storage have shown great potential to lengthen the current period of viability of thoracic organs while outside the body, promising better utilization rates, increased donation distance, and improved matching of donors to recipients. Ex-situ organ perfusion (ESOP) can also make some novel therapeutic strategies viable, and the combination of the ESOP platform with such reconditioning therapies endeavors to better improve functional preservation of organs in addition to making more organs viable for transplantation. Given the abundance of clinical and pre-clinical studies surrounding reconditioning of thoracic organs in combination with ESOP, we summarize in this review important concepts and research regarding thoracic organ machine perfusion in combination with reconditioning therapies.

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BACKGROUND: Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain. OBJECTIVES: To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS. CONCLUSIONS: The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong).

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To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.

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BACKGROUND: Normothermic machine perfusion (NMP) is a technique that maintains organs ex situ with normal metabolism, and organ function can be better preserved. The study of multiple-organ NMP is rarely reported. Multiple organ block (MOB) is a self-perfusing system for maintaining multiple organs ex situ, and porcine MOBs have been successfully preserved for 18 to 37 h. Due to the above context, we conceived to maintain abdominal multiple organ block (AMOB) ex situ utilizing NMP technology. METHODS: AMOBs were procured from Ba-Ma miniature pigs through en bloc procurement surgery. The process of cold preservation was eliminated between the procurement and machine perfusion, and a few minutes of warm ischemia emerged. Autologous whole blood was collected during procurement surgery as a perfusate component in the beginning. RESULTS: The median time of procurement surgery was approximately 220 min, and the median time of warm ischemia was 300 sec. Cases 1 and 2 suffered from repeated hypotension during the procurement surgery, and case 2 exhibited hemorrhage. After improved and optimized procurement processes, the vital signs of cases 3 to 5 remained stable during procurement. In the NMP phase, the flow increased slowly in cases 1 and 2 and did not remain stable even after continuous infusion of a high-dose vasodilator. The lactic acid level rapidly increased, and the levels of ALT and AST were obviously higher than those in cases 3 to 5. In contrast, the flow rate increased smoothly in cases 3 to 5. The lactic acid level remained stable during the first 10 h of perfusion. CONCLUSIONS: AMOB procurement from heart-beating pigs for NMP without initial cold preservation is technically feasible.

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Recent advancement in organ perfusion technology has led to increase clinical transplantation of marginal donor organs and allow for distant procurement of cardiac allograft beyond the time limitation of cold static storage. Ex-situ heart perfusion also provides essential nutrients to maintain cell integrity, thereby reducing the risk of ischaemic injury for functional preservation and provides a platform to assess organ viability and feasibility, with the potential for pharmacotherapy to recover these hearts. Notably, the use of NMP has led to the first distant procurement cardiac transplantation from a donation after circulatory death (DCD) in 2014, which resulted in the adoption of DCD heart transplantation in 4 centres between the United Kingdom and Australia. To date, over 100 DCD heart transplants have been performed utilising cardiac perfusion system with an estimated 10-15% increase in transplant activity in the individual units. This review aims to provide an overview of current experience and outcomes using cardiac perfusion technology, including future technologies and recent advancement within the field.

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BACKGROUND: Type 2 donation after cardiac death (DCD) represents an underused source of grafts for liver transplantation. In our center, normothermic regional perfusion and strict selection criteria have led to acceptable postoperative results after transplanting type 2 DCD livers. However, many of these grafts are still discarded before transplantation. We believe that the suitability of these organs may be improved by adding normothermic machine perfusion (NMP) to our current procedure. MATERIALS AND METHODS: A total of 5 type 2 DCD livers discarded for transplantation were submitted to normothermic regional perfusion and 12 h of NMP. The macroscopic aspect of the liver, vascular and bile flows, and pH were continuously monitored. Serial perfusate analyses and liver biopsies were performed. After NMP, the microscopic appearance of the liver parenchyma and the bile ducts was analyzed. RESULTS: All the grafts showed hemodynamic stability during the NMP. The alanine aminotransferase peak during NMP correlated with the warm ischemia time (Pearson correlation of 0.933, p 0.021). After an initial period of acidosis, the grafts were generally able to spontaneously correct pH and lactate levels without the need for additional bicarbonate. Livers with favorable bile duct histology generally started bile production earlier and registered higher bile flows. CONCLUSIONS: NMP represents a feasible procedure for use with type 2 DCD livers. The pH and lactate correction and the bile flows appear to be significant factors associated with graft viability. However, these favorable results should be confirmed in a clinical transplant setting.

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