The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence.
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ABSTRACT:
SUBMITTER: Maspero M
PROVIDER: S-EPMC10523008 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence.
Maspero Marianna M Yilmaz Sumeyye S Cazzaniga Beatrice B Raj Roma R Ali Khaled K Mazzaferro Vincenzo V Schlegel Andrea A
JHEP reports : innovation in hepatology 20230711 11
The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of pe ...[more]
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Project description:Liver ischemia-reperfusion injury (IRI) is a major complication of liver trauma, resection, and transplantation. IRI may lead to liver dysfunction and failure, but effective approach to address it is still lacking. To better understand the cellular and molecular mechanisms of liver IRI, functional roles of numerous cell types, including hepatocytes, Kupffer cells, neutrophils, and sinusoidal endothelial cells, have been intensively studied. In contrast, hepatic stellate cells (HSCs), which are well recognized by their essential functions in facilitating liver protection and repair, have gained less attention in their role in IRI. This review provides a comprehensive summary of the effects of HSCs on the injury stage of liver IRI and their associated molecular mechanisms. In addition, we discuss the regulation of liver repair and regeneration after IRI by HSCs. Finally, we highlight unanswered questions and future avenues of research regarding contributions of HSCs to IRI in the liver.
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Project description: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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