Optimal utilization of extended hepatic grafts

Abstract

Orthotopic liver transplantation has emerged as the standard treatment for end-stage liver disease. In the United States, the number of listed patients has tripled in the last two decades. Organ availability during the same period has plateaued at approximately 6000 grafts annually, resulting in a fivefold increase in wait-list mortality. The problem is not specific to the United States; European and Asian registries report similar shortages. Donor pool expansion strategies such as the use of living donors, cadaveric split livers, and "extended criteria donors"; (ECD) are being pursued. Used judiciously, ECD grafts provide an opportunity for addressing the shortage. Although there is no universally accepted definition of ECD, the term generally refers to donor factors predisposing recipients to poor initial graft function and/or increased long-term risk. These factors include advanced donor age, hypernatremia, prolonged warm ischemic time, pressor requirement, and donation after cardiac death. The transplant community is scrutinizing all factors to evaluate the degree of risk they impart on the recipient and the extent to which grafts can be "matched"; to maintain acceptable outcomes. We review the importance of selected factors and the impact of a "matching"; strategy to minimize recipient risk while optimizing graft use.

Initial Poor Graft Dysfunction and Primary Graft Non-Function After Orthotopic Liver Transplantation

“…Recently, an analysis of OPTN/UNOS data demonstrates donor age > 60 years, WIT > 30 minutes, CIT > 10 hours, retransplantation, and recipient cardiopulmonary support pre-OLT to be the most important predictors of significantly PGNF and patient survival after transplantation of a DCD graft (Mateo et al, 2006). Similarily, the University of California, Los Angeles (UCLA) reported with controlled DCD that PGNF occurred only in 2.6% of the recipients with about 30 minutes of mean WIT (Gordon Burroughs & Busuttil, 2009). …”

“…Hepatic graft from old donor may increase susceptibility to cold ischemia-induced endothelial injury with impaired adenosine triphosphate (ATP) synthesis post reperfusion and result in decreased regenerative capacity and synthetic function (Gordon Burroughs & Busuttil, 2009). Donor age has been a well-recognized factor affecting PGNF.…”

“…Macrovesicular steatosis may impaire mitochondrial oxidation of fatty acids, increase synthesis and delivery of fatty acids to hepatocytes, reduce the removal of hepatocyte triglycerides, and microcirculatory disruption with narrowing of the hepatic sinusoids by enlarged, fat-laden hepatocytes (Reddy & Rao, 2006). Further more, macrovesicular steatosis may increase the oxidative injury of endothelial cell and hepatocyte and the vulnerability to secondary insults, including the cytokine surge associated with brain death as well as cold ischemic injury (Gordon Burroughs & Busuttil, 2009). In addition, the occurrence of IPGF or PGNF may be due to the release of free lipids from fatty hepatocytes, probably as a consequence of cold ischemia.…”

Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis

“…A universally accepted definition of extended-criteria donors (ECDs) is still lacking, although it generally refers to the presence of donor factors that are associated with poor graft function and a heightened risk for graft loss. To this regard, advanced donor age, steatosis, hypernatremia, prolonged cold (CIT) and warm ischemic times (WIT), inotropic drug requirement, a longer intensive care unit (ICU) stay, DCD, history of malignancies and a positive viral serology are the most important independent risk factors for graft loss after LT (2).…”

Changing Pattern of Donor Selection Criteria in Deceased Donor Liver Transplant: A Review of Literature

“…11 Though priority in liver allocation is based on the Model for End-Stage Liver Disease (MELD) score, donor-recipient matching occurs at the time of organ procurement and transplantation, and substantial selection is involved in accepting an organ. 12 The identification of donor-related factors that portend poor posttransplant outcomes and analysis that can guide the use of organs according to donor characteristics have become increasingly important, 13 especially because donor characteristics and medical management vary by region and organ procurement organization and may affect posttransplant outcomes.…”