Mechanistic Insight and Clinical Implications of Ischemia/Reperfusion Injury Post Liver Transplantation

Abstract

Ischemia/reperfusion injury is an inevitable process during liver transplantation and can lead to a high incidence of early allograft dysfunction and graft failure. The mechanism of hepatic ischemia/reperfusion injury has been elucidated as the sequelae of microcirculation dysfunction, hypoxia, oxidative stress, and cell death. In addition, the essential role of innate and adaptive immune response in hepatic ischemia/reperfusion injury and its deleterious outcomes have been discovered. Furthermore, mechanistic studies of living donor liver transplantation have elucidated distinct features of mitochondrial and metabolic dysfunction in steatotic and small-for-size graft injury. The mechanistic findings of hepatic ischemia/reperfusion injury have laid the foundation for exploring new biomarkers; however, they are yet to be validated in large cohorts. Moreover, the molecular and cellular mechanistic analysis of hepatic ischemia/reperfusion injury has promoted the development of potential therapeutics in preclinical and clinical trials. This review summarizes the most up to date evidence for liver ischemia/reperfusion injury and puts forward the importance of the spatiotemporal microenvironment that results from microcirculation dysfunction, hypoxia, metabolic dysfunction, oxidative stress, innate immunologic response, adaptive immunity, and cell death signaling.

Keywords: Biomarker; Ischemia/Reperfusion Injury; Liver Transplantation; Therapy.