Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation: A Time-to-Rejection Analysis

BACKGROUND: The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes. METHODS: Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular rejections (ACRs) in 46 adult recipients who underwent LT between 2010 and 2014 at our institute. Cox regression models were used to study relevant risk factors in order to estimate hazard ratios for episodes of rejection after LT. RESULTS: Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NK T cellular subset (P = 0.001). The length of follow-up after LT was 41.0 ± 20.9 months, and 11 (23.9%) recipients experienced biopsy-proven ACR. At time-to-rejection proportional regression analysis, a cutoff value of 33.7% was optimal, with a sensitivity of 1, specificity of 0.57, and positive and negative predictive values of 0.42 and 1, respectively. The liver perfusate NK cell subset was strongly associated with biopsy-proven ACR (hazard ratio, 10.7; P = 0.02). CONCLUSIONS: Liver perfusate cytofluorimetric phenotyping may contribute as a targeted preoperative tool to predict the risk of ACR, and as clinical test in translational studies that aim to improve donor allograft procurement and transplant outcomes.