Deceased organ donation includes donation after circulatory death (CD) and donation after brain death (BD). Most organs (80%) submitted to liver transplantation (LT) originate from BD donors and 4 to 20% from CD donors. CD and BD cause important hemodynamic changes, hypoperfusion in the mesenteric microcirculation, and warm hepatic ischemia, that lead to inflammation and cell death, and results in injurious effects on liver grafts used for transplantation.

To reduce mortality on the waiting list, the use of marginal livers grafts could expand the donor pool in cadaveric donors. There are two categories of marginal livers: livers with a high risk of technical complications and impaired function (i.e. elderly donors, steatotic donors, obese or diabetic donors or split livers), and grafts entailing the risk of infection or malignancy for the recipient (i.e. donor with viral infections or cancer). In the coming years, there will be a need to use liver grafts from donors with such pathologies to reduce the waiting-list for transplant and the presence of metabolic pathologies in liver resection will be so recurrent.

Therapeutic strategies are urgently required to reduce the deleterious effects of BD and CD on liver grafts, the poor tolerance of marginal livers to I/R injury, and regenerative failure in resections and LT. Despite numerous studies, the impact of each marginal donor variable on graft function, recipient survival, or post-surgical outcomes after liver surgery is still under investigation because of contradictory results. Moreover, molecular aspects of the harmful effects of BD and CD in liver grafts that undergo transplantation are poorly described. Knowledge is needed about which are the common molecular signaling mechanisms underlying the different liver pathologies, BD and CD, and that also plays a role in hepatic I/R. Discussions on these aspects are highly relevant as it is the basis to develop effective targets to improve the postoperative outcomes when a pathological liver undergoing transplantation or resection, and when deceased organ donation occurs. Such therapies would allow the use of grafts from extended criteria donors thus reducing the waiting-list for transplant, and also would lead to better post-surgical outcomes for pathological livers undergoing resection. These advances would improve the clinical prognosis of liver surgery in the coming years. As LT is an emergency surgery, advances about quick and non-invasive tools to determine the degree of steatosis and the presence of liver pathologies in the donor (which seriously compromises the prognosis in LT), prior to implantation in the recipient, are required for the establishment of new useful approaches in LT.

This Research Topic aims to include basic, translational, and clinical Original Research, Review, Systematic Review, Brief Research Report, Case Reports, and Mini-reviews focusing on the following topics:

· Management protocols for donors from extended criteria.

· Signaling pathways responsible for the poor tolerance of marginal livers to hepatic I/R injury and regeneration failure.

· Identification of therapeutic targets to improve the postoperative outcomes of liver grafts from extended criteria donors.

· Clinical effects of pharmacological treatments and surgical strategies in the surgery of pathological livers.

· Underlying molecular mechanisms for obesity, MetS, insulin resistance or diabetes that negatively affect the post-operative outcomes in resections or LT.

· Non-invasive techniques to determine degree of steatosis and the presence of concurrent metabolic pathologies in liver grafts before their implantation in the recipient.

· Prognostic biomarkers in patients subjected to liver resection or transplantation to monitor the progression of liver damage.

· Effects of BD or CD on liver grafts.

· Research in hepatic warm ischemia evaluating potential therapeutic strategies that could be useful in liver resection or transplantation.

· Research about I/R injury, BD or CD effects on different abdominal organs such as intestine or kidney, addressing how findings in such organs could affect liver function.

Acknowledgment: We would like to acknowledge Ph.D. student Marc Micó-Carnero who has contributed to the preparation of the proposal for this Research Topic and who will act as Research Topic Coordinator

Impact

Frontiers in Medicine

Gastroenterology