Experimental Brain Death Models in Liver Transplantation

Most organs for transplantation are currently procured from brain-dead donors; however, brain death is an important risk factor in liver transplantation. In addition, to counteract the shortage of liver grafts, transplant centers accept the use of sub-optimal livers, which may show higher risk of primary non-function or initial poor function. Very few literatures exist regarding liver transplantation using brain-dead donors, or about brain death and its effects on sub-optimal grafts in such surgical situation. This chapter aims to describe the pathophysiological changes occurring in liver grafts during brain death and focuses on the strengths and limitations of experimental models used to study the effect of brain death on optimal and sub-optimal (specially steatotic) liver grafts. Depending on the use of experimental models that simulate as much as possible the surgical conditions present in clinical practice, therapeutic strategies designed in animal models could be more successfully translated to the bedside

Ischemic Preconditioning Directly or Remotely Applied on the Liver to Reduce Ischemia-Reperfusion Injury in Resections and Transplantation

Ischemia-reperfusion (I/R) injury is an important cause of liver damage occurring during surgical procedures. In liver resection, I/R causes post-operative transaminasemia and liver function failure. In liver transplantation, I/R causes graft dysfunction, ranging from biochemical abnormalities to primary non-function of the transplanted organ. Ischemic preconditioning is a surgical strategy to reduce the severity of I/R and improve post-operative outcomes by prior exposure to a brief period of vascular occlusion directly to the target organ or remotely to a distant vascular bed. This chapter aims to discuss the different ischemic preconditioning strategies in both liver resection surgery and liver transplantation. In addition, we will describe the differences of such surgical strategies in both steatotic and non-steatotic livers in both preclinical experiments and clinical practice. Such information may be useful to guide the design of the effective ischemic preconditioning methods in the surgery of hepatic resections and liver transplantation

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

Ischemia-reperfusion (I/R) associated with hepatic resection and living related liver transplantation is an unsolved problem in clinical practice. Indeed, I/R induces damage and regenerative failure in clinical liver surgery. Signaling pathways regarding the pathophysiology of liver I/R and regeneration making clear distinction between situations of cold and warm ischemia, as well as liver regeneration with or without vascular occlusion, will be addressed. The different experimental models used to date to improve the postoperative outcomes in clinical liver surgery will be also described. Furthermore, the most updated therapeutic strategies, as well as the clinical and scientific controversies in the field, will be discussed. Such information may be useful to guide the design of better experimental models as well as the effective therapeutic strategies in liver surgery that can succeed in achieving its clinical application

New Perspectives on the Use of Sub-Optimal Donor Livers

Liver transplantation is the therapy of choice for patients with end-stage liver disease. However, a shortage of donor organs remains a major obstacle to the widespread application of liver transplantation. To overcome this problem, transplant centers have developed strategies to expand the organ donor pool, including the routine use of sub-optimal donor livers. However, these have an increased risk of initial poor function or primary non-function that may cause greater risk of morbidity in the recipient. This chapter aims to describe the pathophysiological changes that may occur in sub-optimal donor livers, focusing on viral infections, since, after transplantation, infection of the graft is almost universal and can lead to chronic hepatitis, cirrhosis, and graft failure. The different experimental models as well as the clinical outcomes of the transplantation of sub-optimal donor livers with viral infections will be discussed. Such information may be useful to guide the design of better experimental models than those described to date as well as the effective use of sub-optimal livers with successful clinical application