Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma

Abstract

The major extended donor criteria (maEDC; steatosis >40%, age >65 years, and cold ischemia time >14 h) influence graft and patient outcomes after liver transplantation. Despite organ shortages, maEDC organs are often considered unsuitable for transplantation. We investigated the outcomes of maEDC organ liver transplantation in patients with hepatocellular carcinoma (HCC). Two hundred and sixty-four HCC liver transplant patients were eligible for analysis. Risk factor analysis was performed for early allograft dysfunction; primary nonfunction; 30-day and 90-day graft failure; and 30-day, 90-day, and 1-year patient mortality. One-year graft survival was higher in recipients of no-maEDC grafts. One-year patient survival did not differ between the recipients of no-maEDC and maEDC organs. The univariate and multivariate analyses revealed no association between maEDC grafts and one-year patient mortality. Graft survival differed between the recipients of no-maEDC and maEDC organs after correcting for a laboratory model of end-stage liver disease (labMELD) score with a cut-off value of 20, but patient survival did not. Patient survival did not differ between recipients who did and did not meet the Milan criteria and who received grafts with and without maEDC. Instead of being discarded, maEDC grafts may expand the organ pool for patients with HCC without impairing patient survival or recurrence-free survival.

The Differential Influence of Cold Ischemia Time on Outcome After Liver Transplantation for Different Indications—Who Is at Risk? A Collaborative Transplant Study Report

“…This clearly suggests that with the increase of the MELD score, the tolerance of prolonged cold ischemia decreases. Because allocating grafts with longer CIT to the aforementioned recipient category did not carry disproportionate risk, this type of matching (longer CIT with HCC recipients and MELD < 20) is in line with previous findings and may be acceptable when facing organ shortage (2,5). Patient survival constantly better than graft survival, also after longer CIT, was observed only in recipients with HCC.…”

“…This may be attributed to the higher resilience of a re-transplant in patients with HCC. While Goldaracena et al showed that patients with high labMELD scores benefit from transplantation as soon as possible and irrespective of the organ quality, our two recent studies pointed out that exact match between graft and recipient is important, and that grafts with maEDC could be allocated to low-risk patients with labMELD <20 e.g., patients with HCC (2,5,22). These findings were confirmed in a recent large cohort CTS study (8).…”

“…Grafts transplanted into HCV patients appeared to have the lowest tolerance for cold ischemia and were already at a significantly increased risk of graft loss at CIT as low as 8 h. The mechanisms that determine the association between worse outcomes in HCV patients and longer CIT are multifactorial. Together with advanced donor age and macrovesicular steatosis, CIT, as the third maEDC, is an independent risk factor associated with preservation injury, delayed graft function, and biliary complications (2,5). Preservation injury during cold storage affects post-transplant outcomes strongly, especially in HCV recipients because HCV patients with biopsy-proven preservation injury have been shown to have worse outcomes than HCV recipients without histologically proven injury (16,17).…”

“…Because of the chronic organ shortage in most countries and in Eurotransplant, less than optimal, extended donor criteria (EDC) grafts are used to expand the organ pool (2,4). Cold ischemia time (CIT) is a factor that occurs during the allocation and it is considered a major extended donor criterion (maEDC) that affects graft and patient survival along with macrovesicular steatosis and donor age (2,5). Cold ischemia increases the risk of graft failure and early HCC recurrence, and graft outcome depends on its ability to recover from the ischemia injury (2,6,7).…”

“…Although the awareness of the negative impact of CIT has generally increased, the information on CIT's influence on outcome of maEDC grafts is scarce. Moreover, the accepted limits for CIT are subject to regional differences (5,(8)(9)(10). This study aimed to identify liver transplant recipients whose grafts are less affected from a prolonged cold ischemia, and to describe risk factors associated with an adverse outcome following transplantation of such organs.…”