The 24-hour normothermic machine perfusion of discarded human liver grafts.

Donor organ shortage necessitates use of less than optimal donor allografts for transplantation. The current cold storage preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation (NMP) of liver allografts. In this study, we analyze discarded human liver grafts that underwent NMP for the extended period of 24 hours. Thirteen human liver grafts which had been discarded for transplantation were entered into this study. Perfusion was performed with an automated device using an oxygenated, sanguineous perfusion solution at normothermia. Automated control was incorporated for temperature-, flow-, and pressure-regulation as well as oxygenation. All livers were perfused for 24 hours; parameters of biochemical and synthetic liver function as well as histological parameters of liver damage were analyzed. Livers were stratified for expected viability according to the donor's medical history, procurement data, and their macroscopic appearance. Normothermic perfusion preservation of human livers for 24 hours was shown to be technically feasible. Human liver grafts, all of which had been discarded for transplantation, showed levels suggesting organ viability with respect to metabolic and synthetic liver function (to varying degrees). There was positive correlation between instantly available perfusion parameters and generally accepted predictors of posttransplant graft survival. In conclusion, NMP is feasible reliably for periods of at least 24 hours, even in highly suboptimal donor organs. Potential benefits include not only viability testing (as suggested in recent clinical implementations), but also removal of the time constraints associated with the utilization of high-risk livers, and recovery of ischemic and other preretrieval injuries (possibly by enabling therapeutic strategies during NMP). Liver Transplantation 23 207-220 2017 AASLD.

Vogel T ，Brockmann JG ，Quaglia A ，Morovat A ，Jassem W ，Heaton ND ，Coussios CC ，Friend PJ ... -  《-》

A Back-to-Base Experience of Human Normothermic Ex Situ Liver Perfusion: Does the Chill Kill?

Normothermic machine perfusion (NMP) has been shown to protect livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back-to-base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back-to-base livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30-day patient and graft survival. A total of 46 liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ perfusion function. The 30-day patient and graft survival in the back-to-base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back-to-base livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back-to-base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.

Bral M ，Dajani K ，Leon Izquierdo D ，Bigam D ，Kneteman N ，Ceresa CDL ，Friend PJ ，Shapiro AMJ ... -  《-》

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers.

Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. Liver Transplantation 22 979-993 2016 AASLD.

Banan B ，Watson R ，Xu M ，Lin Y ，Chapman W ... -  《-》

Impact of machine perfusion preservation of liver grafts from donation after cardiac death.

Because of the critical shortage of deceased donor grafts, using a donation after cardiac death (DCD) donor is an important resource. However, the ischemic damage of those DCD grafts jeopardizes organ viability during cold storage. Maintaining organ viability after donation until transplantation is important for optimal graft function and survival. This review describes the effective preservation in transplantation for DCD livers. Concepts and development of machine perfusion for DCD liver grafts to reduce ischemia/reperfusion injury are discussed. Despite the fact that hypothermic machine perfusion might be superior to static cold preservation, DCD livers are exposed to hypothermia-induced damage. Recently, some groups introduced the beneficial effects of normothermic or subnormothermic machine perfusion in DCD liver preservation and transplantation.

Matsuno N ，Uchida K ，Furukawa H 《-》

Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial.

van Leeuwen OB ，de Vries Y ，Fujiyoshi M ，Nijsten MWN ，Ubbink R ，Pelgrim GJ ，Werner MJM ，Reyntjens KMEM ，van den Berg AP ，de Boer MT ，de Kleine RHJ ，Lisman T ，de Meijer VE ，Porte RJ ... -  《-》