Evaluation of Liver Quality after Circulatory Death versus Brain Death: A Comparative Preclinical Pig Model Study

Abstract

The current organ shortage in hepatic transplantation leads to increased use of marginal livers. New organ sources are needed, and deceased after circulatory death (DCD) donors present an interesting possibility. However, many unknown remains on these donors and their pathophysiology regarding ischemia reperfusion injury (IRI). Our hypothesis was that DCD combined with abdominal normothermic regional recirculation (ANOR) is not inferior to deceased after brain death (DBD) donors. We performed a mechanistic comparison between livers from DBD and DCD donors in a highly reproducible pig model, closely mimicking donor conditions encountered in the clinic. DCD donors were conditioned by ANOR. We determined that from the start of storage, pro-lesion pathways such as oxidative stress and cell death were induced in both donor types, but to a higher extent in DBD organs. Furthermore, pro-survival pathways, such as resistance to hypoxia and regeneration showed activation levels closer to healthy livers in DCD-ANOR rather than in DBD organs. These data highlight critical differences between DBD and DCD-ANOR livers, with an apparent superiority of DCD in terms of quality. This confirms our hypothesis and further confirms previously demonstrated benefits of ANOR. This encourages the expended use of DCD organs, particularly with ANOR preconditioning.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study)

“…Similarly, high-volume centers in Taiwan and India have reported comparable 5-year OS for LDLT in high-MELD candidates in contrast to low-MELD score recipients [ 25 , 30 ]. In addition, a living-donor liver allograft is not exposed to brain death, which not only alters the quality of the donor organ but may also negatively affect both graft and patient survival [ 62 , 63 ].…”

Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde?

“…Currently, liver transplantation (LT) remains an unsolved problem in clinical practice, not only due to the lack of donor grafts but also because of the risk factors of liver dysfunction or failure that show steatotic livers (present in 30% of total liver grafts) [1] or livers from a brain-dead (BD) donor (the 80% of deceased donors) [2]. BD negatively affects the hepatic function following transplantation [3,4], and livers with steatosis are more susceptible to ischemia-reperfusion (IR) injury, thus negatively affecting liver function and graft quality [5]. Therefore, many liver grafts are discarded, exacerbating the shortage of grafts [2,6].…”