The Role of Adipokines in Surgical Procedures Requiring Both Liver Regeneration and Vascular Occlusion

Abstract

Liver regeneration is a perfectly calibrated mechanism crucial to increase mass recovery of small size grafts from living donor liver transplantation, as well as in other surgical procedures including hepatic resections and liver transplantation from cadaveric donors. Regeneration involves multiple events and pathways in which several adipokines contribute to their orchestration and drive hepatocytes to proliferate. In addition, ischemia-reperfusion injury is a critical factor in hepatic resection and liver transplantation associated with liver failure or graft dysfunction post-surgery. This review aims to summarize the existing knowledge in the role of adipokines in surgical procedures requiring both liver regeneration and vascular occlusion, which increases ischemia-reperfusion injury and regenerative failure. We expose and discuss results in small-for-size liver transplantation and hepatic resections from animal studies focused on the modulation of the main adipokines associated with liver diseases and/or regeneration published in the last five years and analyze future perspectives and their applicability as potential targets to decrease ischemia-reperfusion injury and improve regeneration highlighting marginal states such as steatosis. In our view, adipokines means a promising approach to translate to the bedside to improve the recovery of patients subjected to partial hepatectomy and to increase the availability of organs for transplantation.

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

“…Some of the more well‐known members of this family include IL‐6, adiponectin and leptin. In a comprehensive review, Peralta and colleagues examined the available data regarding adipokines and concluded that there was sufficient evidence to suggest that these molecules had a role in liver regeneration after IRI, particularly IL‐6, but that more data in partial ischaemia and steatotic liver injury models were required to clearly establish the positive or negative effects of the more than 600 adipokines known to date …”

Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery

“…Patients with end-stage liver diseases who undergo LT usually present with malnutrition, which directly impacts the deterioration of the patient's clinical condition, affecting post-transplantation survival [24]. The post-transplantation survival is even more relevant in the case of liver steatosis (the main feature of NAFLD) as these organs show high vulnerability to I/R injury and regenerative failure in comparison with non-steatotic livers [53].…”

“…Most studies based on nutrients and dietary supplements reported benefits on liver function and oxidative stress parameters, but we did not find many studies aimed to improve liver regeneration (six of 20) and only three reported improvements in this parameter. As steatotic grafts show increased vulnerability to I/R when they are transplanted and pre-existing steatosis is related with impairment of liver regeneration following PH [53,141], more than the only three studies performed in steatotic liver seems to be warranted. We only found one study reporting the use of probiotics as a strategy.…”

Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection

“…After partial resection, liver regeneration is a perfectly regulated and highly coordinated response whose apparent sensor is the need to modify the size of the remaining liver; it involves the action of several growth factors [ 28 , 29 ]. Liver regeneration progression is composed by three main phases: (1) The priming stage, (2) proliferation stage, and (3) termination stage.…”

“…However, there is evidence obtained from PH studies that VEGF levels increase after surgery, and that the infusion of VEGF can decrease injury and increase hepatocyte proliferation [ 93 , 94 , 95 ]. The latter is required in liver surgery since I/R reduces liver regeneration and is also associated with post-surgical liver failure or graft dysfunction [ 28 ]. VEGF protective effects on liver injury and liver regenerative failure have been observed in non-steatotic livers subjected to PH with vascular occlusion.…”