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

  • Jiang Liu
    Affiliations
    Department of Surgery, HKU-Shenzhen Hospital & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong

    Hepato-pancreato-biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
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  • Kwan Man
    Correspondence
    Correspondence: Kwan Man, Tel.: (852)39179646, Fax: (852)39179634, , Address: L9-55, Lab block, 21 Sassoon Road, Pokfulam, Hong Kong
    Affiliations
    Department of Surgery, HKU-Shenzhen Hospital & LKS Faculty of Medicine, The University of Hong Kong, Hong Kong
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Open AccessPublished:March 17, 2023DOI:https://doi.org/10.1016/j.jcmgh.2023.03.003
Mechanistic Insight and Clinical Implications of Ischemia/Reperfusion Injury Post Liver Transplantation
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      Abstract

      Ischemia/reperfusion injury is an inevitable process during liver transplantation and can lead to a high incidence of early allograft dysfunction (EAD) 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 put forward the importance of the spatio-temporal microenvironment that results from microcirculation dysfunction, hypoxia, metabolic dysfunction, oxidative stress, innate immunologic response, adaptive immunity, and cell death signaling.

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      Article info

      Publication history

      Accepted: March 10, 2023
      Received in revised form: March 10, 2023
      Received: December 5, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Grant Support: This study was supported by the Research Grafts Council of University Grants Committee of Hong Kong (C7021-21G, T12-703/19-R, 17124219, 17106921).

      Disclosures: The authors have no conflict of interest to disclose.

      Author Contributions: Study concept and design: Kwan Man, Jiang Liu; Literature search and review: Jiang Liu; Drafting of the manuscript: Jiang Liu; Critical revision: Kwan Man.

      Synopsis

      Hepatic ischemia/reperfusion injury post liver transplantation is characterized as spatio-temporal microenvironmental disturbance including microcirculatory dysfunction, metabolic dysregulation, oxidative stress, innate and adaptive immunologic response and cell death signaling. The mechanistic understanding enables novel biomarkers and therapeutics development in preclinical models and clinical trials.

      Identification

      DOI: https://doi.org/10.1016/j.jcmgh.2023.03.003

      Copyright

      © 2023 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.

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