Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2021; 13(5): 533-542
Published online May 27, 2021. doi: 10.4254/wjh.v13.i5.533
Direct, remote and combined ischemic conditioning in liver surgery
Rafał Stankiewicz, Michał Grąt
Rafał Stankiewicz, Michał Grąt, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw 02-097, Poland
Author contributions: Stankiewicz R conceptualized the study, did the literature search, wrote the paper and approved the final version of the article; Grąt M conceptualized the study, did the literature search, critically reviewed the paper and approved the final version of the article.
Supported by National Science Centre, Poland, No. 2019/34/E/NZ5/00433.
Conflict-of-interest statement: Grąt M reports grants from the National Science Centre, Poland during the conduct of the study; Stankiewicz R has none to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Rafał Stankiewicz, MD, PhD, Surgeon, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 1A Banacha Street, Warsaw 02-097, Poland.
Received: February 17, 2021
Peer-review started: February 17, 2021
First decision: March 16, 2021
Revised: March 28, 2021
Accepted: May 7, 2021
Article in press: May 7, 2021
Published online: May 27, 2021

Liver ischemia-reperfusion injury is a major cause of postoperative liver dysfunction, morbidity and mortality following liver resection and transplantation. Ischemic conditioning has been shown to ameliorate ischemia-reperfusion injury in small animal models. It can be applied directly or remotely when cycles of ischemia and reperfusion are applied to a distant site or organ. Considering timing of the procedure, different protocols are available. Ischemic preconditioning refers to that performed before the duration of ischemia of the target organ. Ischemic perconditioning is performed over the duration of ischemia of the target organ. Ischemic postconditioning applies brief episodes of ischemia at the onset of reperfusion following a prolonged ischemia. Animal studies pointed towards suppressing cytokine release, enhancing the production of hepatoprotective adenosine and reducing liver apoptotic response as the potential mechanisms responsible for the protective effect of direct tissue conditioning. Interactions between neural, humoral and systemic pathways all lead to the protective effect of remote ischemic preconditioning. Despite promising animal studies, none of the aforementioned protocols proved to be clinically effective in liver surgery with the exception of morbidity reduction in cirrhotic patients undergoing liver resection. Further human clinical trials with application of novel conditioning protocols and combination of methods are warranted before implementation of ischemic conditioning in day-to-day clinical practice.

Keywords: Ischemic preconditioning, Ischemia-reperfusion injury, Hepatectomy, Liver transplant, Morbidity, Mortality

Core Tip: The concept of ischemic conditioning seems easy to apply and is an inexpensive method with the potential to protect the liver during hepatic surgery. It covers a wide spectrum of techniques and allows adjustment of the method to the particular patient. Unfortunately, despite promising animal studies in preventing ischemia-reperfusion injury by ischemic conditioning, currently there is a lack of sufficient data on its clinical efficacy in humans.