Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma (HCC). However, cancer recurrence, posttransplantation, remains to be the critical issue which affects the long-term outcome of HCC recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute phase liver graft injury is a result of hepatic ischemia reperfusion (I/R) injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death (DCD), and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating tumor cell invasion and migration, but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic I/R injury on tumor recurrence posttransplantation, both in clinical and animal cohorts. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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