Liver transplantation has been identified as the most effective treatment for patients with end-stage
liver diseases. However, hepatic
ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post
transplantation. Cell death, including apoptosis,
necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and
mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft
inflammation. The
inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection,
cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of
inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of
cancer recurrence and fibrogenesis due to the long-term impact of
inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including
ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.