Abstract
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.
Key Points
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The cellular damage incurred by organ procurement and preservation affects transplantation outcomes, contributes to donor organ shortage and represents a major risk factor for acute and chronic liver graft rejection
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Liver ischaemia–reperfusion injury (IRI) is a local proinflammatory response that is mediated by the innate immune system
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Several pattern recognition receptors, including Toll-like receptor (TLR)4, TLR9 and the inflammasome, are involved in liver immune activation against ischaemia–reperfusion in distinct cell types at different stages of IRI development
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Different subsets of T cells participate in innate immune responses triggered by ischaemia–reperfusion via positive and negative co-stimulatory pathways
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Studies of regulated hepatic reperfusion in large animals might lead to successful clinical use of liver grafts procured from extended criteria donors and donation after cardiac death
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Change history
11 January 2013
In the version of this article initially published online the animal model in Figure 3 was portrayed incorrectly. The error has been corrected for the print, HTML and PDF versions of the article.
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All authors contributed equally to researching data for the article, discussions of content and reviewing and editing the manuscript. Y. Zhai, H. Petrowsky, J. C. Hong and J. W. Kupiec-Weglinski wrote the article.
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Zhai, Y., Petrowsky, H., Hong, J. et al. Ischaemia–reperfusion injury in liver transplantation—from bench to bedside. Nat Rev Gastroenterol Hepatol 10, 79–89 (2013). https://doi.org/10.1038/nrgastro.2012.225
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DOI: https://doi.org/10.1038/nrgastro.2012.225
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