Nrf2 Appears to Be Downregulated in Steatotic Compared with Lean Liver Allografts - A Potential Role for Targeted Therapies

Hepatic steatosis (HS) is a key factor predicting postoperative allograft function and determining overall discard in liver transplantation (LT). The potential of normothermic machine perfusion (NMP) as an adjunct to LT has been a focus of recent scrutiny due to its ability to attenuate ischemia reperfusion injuries (IRI) and maintain graft functionality. The nuclear-factor-erythroid 2-related-factor-2 (Nrf2) axis may be an important IRI mediator in HS. We aimed to characterize and compare Nrf2 expression profiles between lean and steatotic tissue undergoing NMP.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Transplantation and tissue engineering Source Type: research

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Purpose of review To review the role of machine perfusion in advancing the study and clinical application of liver xenotransplantation to liver transplantation. Recent findings Recent multicenter trial has shown the benefits of normothermic machine perfusion (NMP) in the assessment and selection of suitable allografts for liver transplantation, especially marginal liver allografts. Advances in ex-vivo therapeutic intervention with proof-of-concept studies demonstrating successful ex-vivo genetic modification of donor allografts and blockade of gene expression with siRNA. Summary Xenotransplantation and NMP are two ...
Source: Current Opinion in Organ Transplantation - Category: Surgery Tags: XENOTRANSPLANTATION: Edited by Parsia A. Vagefi Source Type: research
Background. Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. Methods. In the period October 2018–February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney...
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science—Liver Source Type: research
tschke J Abstract BACKGROUND:  The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed. METHODS:  Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation. RESULTS:  A total of 8594 livers were offered for transplantation,...
Source: Zeitschrift fur Gastroenterologie - Category: Gastroenterology Authors: Tags: Z Gastroenterol Source Type: research
Abstract PURPOSE OF REVIEW: To review the role of machine perfusion in advancing the study and clinical application of liver xenotransplantation to liver transplantation. RECENT FINDINGS: Recent multicenter trial has shown the benefits of normothermic machine perfusion (NMP) in the assessment and selection of suitable allografts for liver transplantation, especially marginal liver allografts. Advances in ex-vivo therapeutic intervention with proof-of-concept studies demonstrating successful ex-vivo genetic modification of donor allografts and blockade of gene expression with siRNA. SUMMARY: Xenotransplan...
Source: Current Opinion in Organ Transplantation - Category: Transplant Surgery Authors: Tags: Curr Opin Organ Transplant Source Type: research
Conclusions: Use of OrganOx metra for the perfusion and transportation of livers prior to transplantation is a cost-effective strategy. Key Points for Decision MakersIntroduction of OrganOx metra into NHS could increase the utilisation of donated livers with patients experiencing lower rates of early allograft dysfunction and adverse events, compared with current practice.Results of the economic analysis indicate that the OrganOx metra is highly likely to be cost-effective and result in improved patient outcomes. PMID: 32729749 [PubMed - as supplied by publisher]
Source: Journal of Medical Economics - Category: Health Management Tags: J Med Econ Source Type: research
AbstractPurpose of ReviewEscalating end-organ disease coupled with stagnant donor pools has begotten global organ shortages. Ex vivo organ perfusion, used briefly in the early days of clinical transplant and then sidelined for decades by static cold storage, has resurged to address this organ paucity. Given the recent prolific application of machine perfusion as a platform for assessment, preservation, and treatment of marginal grafts, this review summarizes salient results from the past 2 –3 years in kidney, liver, lung, heart, pancreas, vascularized composite allograft, and xenograft transplantation.Recent Fin...
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research
Conclusions: Assessment of flavin, a marker of mitochondrial complex I injury, in the perfusate provides a fast prediction of liver graft function and loss during ex situ MP before implantation. This finding may have high clinical relevance, as liver grafts from extended DBD or DCD donors carry considerable risks for recipients. On-line estimation of outcome before implantation would therefore substantially increase safe utilization of liver grafts.
Source: Annals of Surgery - Category: Surgery Tags: ESA PAPERS Source Type: research
CONCLUSIONS Non-invasive investigations of the liver microcirculation and hemoglobin oxygenation were shown to be predictive factors for EAD following liver transplantation. PMID: 31417074 [PubMed - in process]
Source: Annals of Transplantation - Category: Transplant Surgery Authors: Tags: Ann Transplant Source Type: research
Publication date: Available online 12 July 2019Source: Journal of Clinical and Experimental HepatologyAuthor(s): Prafulla V. Jadhav, Sunil Raviraj Kothakota, Madhu Sasidharan, Harish Kareem, Ajith K. NairIntroductionIschemia reperfusion injury (IRI) is an important complication of liver transplant (LT). The donor risk index, which does not incorporate steatosis, includes several variables known to impact on allograft survival. The purpose of this study was to report on donor liver allograft steatosis and its association with severity of IRI.AimThe aim of this study was to determine the effect of type and grade of donor liv...
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
Publication date: Available online 12 July 2019Source: Journal of Clinical and Experimental HepatologyAuthor(s): Prafulla Vishnurao Jadhav, Kothakota Sunil Raviraj, Madhu Sasidharan, Harish Kareem, Ajith K. NairAbstractIntroductionIschemic reperfusion injury (IRI) is an important complication of liver transplant (LT). The donor risk index (DRI), which does not incorporate steatosis, includes several variables known to impact on allograft survival. The purpose of this study was to report on donor liver allograft steatosis and its association with severity of IRI.AimTo determine effect of type and grade of donor liver steato...
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
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