Hepatic Steatosis and Normothermic Perfusion—Preliminary Experiments in a Porcine Model

Jamieson, Russell W.; Zilvetti, Miguel; Roy, Debabrata; Hughes, David; Morovat, Alireza; Coussios, Constantin C.; Friend, Peter J.

doi:10.1097/tp.0b013e318223d817

Cited by 144 publications

(129 citation statements)

References 27 publications

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“…Attempts to defat steatotic rat livers during MMP failed to demonstrate histological, hemodynamic, and metabolic improvements (65), unlike previous defatting studies performed using NMP (66,67). Also, postreperfusion liver microarchitecture and bile production have been shown to be significantly improved when MP is performed at normothermic versus midthermic or sub-normothermic temperatures (45).…”

Section: Smpcontrasting

confidence: 38%

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Ghinolfi

Rreka

Pezzati

et al. 2017

Transl. Gastroenterol. Hepatol.

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Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers, is the second leading cause of cancer-related deaths and the leading cause of death in patients with cirrhosis. Liver transplantation (LT) represents the ideal treatment for selected patients as it removes both the tumor and the underlying cirrhotic liver with 5-year survival rates higher than 70%. Unfortunately, due to tumor characteristics, patient co-morbidities or shortage of organs available for transplant, only 20% of patients can undergo curative treatment. Ex situ machine perfusion (MP) is a technology recently introduced that might potentially improve organ preservation, allow graft assessment and increase the pool of available organs. The purpose of this review is to provide an update on the current role of ex situ liver MP in liver transplantation for HCC patients.

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Section: Smpcontrasting

confidence: 38%

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Ghinolfi

Rreka

Pezzati

et al. 2017

Transl. Gastroenterol. Hepatol.

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“…In a preliminary study using steatotic porcine livers, Jamieson et al showed a 50% reduction in the steatosis level after 48 hours of NELP. (34) Moreover, normothermic perfusion of steatotic livers from obese Zucker rats using a "defatting cocktail" led to a 50% reduction in intracellular lipid content after 3 hours of machine perfusion. (25) In our preliminary experiments, we employed 2 steatotic human livers not suitable for clinical transplantation and used a defatting protocol at the beginning of NELP.…”

Section: Discussionmentioning

confidence: 99%

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

Banan¹,

Watson²,

Xu³

et al. 2016

Liver Transpl

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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. The major limiting factor of using extended criteria donor (ECD) grafts is their greater susceptibility to injury during cold preservation and lower tolerance for ischemia/reperfusion injury (IRI) upon reperfusion. Therefore, ECD grafts have been associated with a higher risk of posttransplant complications such as primary graft nonfunction and chronic cholangiopathy.(1-4) Machine perfusion has been investigated both as a preservation method to reduce IRI in ECD livers and as a method to assess the viability and function of suboptimal grafts prior to transplantation.(5-7)Currently, there are 3 variants of liver machine perfusion that are distinguished by the perfusate temperature: hypothermic, subnormothermic, and normothermic.

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“…Matched control patients were identified as described above; to find two matched controls, preset criteria were extended in some cases, MELD was 12 in NMP versus 14 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) in matched controls (p = 0.55).…”

Section: Donor and Recipient Characteristicsmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

407

412

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Joint first authors. ISRCTN 14355416.The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ) versus , p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.Abbreviations: AST, aspartate transaminase; DBD, donation after brain death; DCD, donation after circulatory death; IRI, ischemia-reperfusion injury; IVC, inferior vena cava; MELD, model for end-stage liver disease; NHSBT, National Health Service Blood and Transplant; NMP, normothermic machine perfusion

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Hepatic Steatosis and Normothermic Perfusion—Preliminary Experiments in a Porcine Model

Cited by 144 publications

References 27 publications

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

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

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

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