Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

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Abstract

Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts.

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A randomized trial of normothermic preservation in liver transplantation

John Karani, Hynek Mergental, M. Zeeshan Akhtar … (2018)

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

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Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.

Kim M Olthoff, Laura Kulik, Benjamin Samstein … (2010)

Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin >or=10mg/dL on day 7, international normalized ratio >or=1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk = 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk = 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function. (c) 2010 AASLD.

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Ischaemia-reperfusion injury in liver transplantation--from bench to bedside.

Henrik Petrowsky, Charles C. Hong, Ronald Busuttil … (2013)

Ischaemia-reperfusion injury (IRI) in the liver, a major complication of haemorrhagic shock, resection and transplantation, is a dynamic process that involves the two interrelated phases of local ischaemic insult and inflammation-mediated reperfusion injury. This Review highlights the latest mechanistic insights into innate-adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischaemia-reperfusion, discusses progress in large animal experiments and examines efforts to minimize liver IRI in patients who have received a liver transplant. The interlinked signalling pathways in multiple hepatic cell types, the IRI kinetics and positive versus negative regulatory loops at the innate-adaptive immune interface are discussed. The current gaps in our knowledge and the pathophysiology aspects of IRI in which basic and translational research is still required are stressed. An improved appreciation of cellular immune events that trigger and sustain local inflammatory responses, which are ultimately responsible for organ injury, is fundamental to developing innovative strategies for treating patients who have received a liver transplant and developed ischaemia-reperfusion inflammation and organ dysfunction.

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Author and article information

Journal

Journal ID (iso-abbrev): JAMA Surg

Title: JAMA surgery

Publisher: American Medical Association (AMA)

ISSN (Electronic): 2168-6262

ISSN (Print): 2168-6254

Publication date (Electronic): March 01 2022

Volume: 157

Issue: 3

Affiliations

[1 ] Massachusetts General Hospital, Boston.

[2 ] Henry Ford Transplant Institute, Detroit, Michigan.

[3 ] Houston Methodist, Houston, Texas.

[4 ] Virginia Commonwealth University, Richmond.

[5 ] University of Virginia, Charlottesville.

[6 ] Tampa General, Tampa, Florida.

[7 ] Johns Hopkins, Baltimore, Maryland.

[8 ] UT Health Science Center, San Antonio, Texas.

[9 ] University of Tennessee Health Science Center, Memphis.

[10 ] UCSF, San Francisco, California.

[11 ] Emory University Hospital, Atlanta, Georgia.

[12 ] University of Minnesota, Minneapolis.

[13 ] University of Washington, Seattle.

[14 ] The Ohio State University, Columbus.

[15 ] Scripps Clinic and Scripps Green Hospital, San Diego, California.

[16 ] University of California, San Diego, La Jolla.

[17 ] Montefiore Medical Center, Bronx, New York.

[18 ] Mount Sinai Health System, New York, New York.

[19 ] University of Nebraska Medical Center, Omaha.

[20 ] University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

[21 ] University of Texas Southwestern Medical Center, Dallas.

Article

Publisher Item ID: 2787486

DOI: 10.1001/jamasurg.2021.6781

PMC ID: 8733869

PubMed ID: 34985503

SO-VID: d38288b0-1fa8-488f-8d1c-d339b78e5387

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Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

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Most cited references 40

A randomized trial of normothermic preservation in liver transplantation

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.

Ischaemia-reperfusion injury in liver transplantation--from bench to bedside.

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