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, 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 (LPs) could help identify risk factors portending adverse LT outcomes. Methods LPs were collected during the back-table surgical time after the procurement procedures for donors after brain death (DBDs). Lymphocytic concentrations and phenotypes were matched with DBD 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 (HRs) for episodes of rejection after LT. Results Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NKT 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 (TTR) proportional regression analysis, A cut-off 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. LP NK cell subset was strongly associated with biopsy-proven ACR (HR = 10.7, P = 0.02). Conclusions LP 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. Authors' contributions: Duilio Pagano*: Concept/design, Data analysis/interpretation, Drafting article. Ester Badami*: Concept/design, Data analysis/interpretation, Drafting article. Pier Giulio Conaldi: Critical revision of article, Approval of article. Aurelio Seidita and Fabrizio di Francesco: Critical revision of article. Alessandro Tropea: Data collection. Rosa Liotta and Gaia Chiarello: Histology revision. Fabio Tuzzolino and Marco Barbàra: Statistics. Angelo Luca: Critical revision of article, Approval of article. Salvatore Gruttadauria: Critical revision of article, Approval of article. *These authors contributed equally to this study. The first author has been selected to receive a Young Investigator Award for the the 2018 Joint International Congress of ILTS, ELITA & LICAGE being held from 23-26 May 2018 in Lisbon, Portugal. Corresponding author: Salvatore Gruttadauria, IRCCS-ISMETT, Via E. Tricomi 5, 90127 Palermo, Italy. Phone +39 091 21 92 111. Fax +39 091 21 92 400. E-mail: sgruttadauria@ismett.edu Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by Transplantation. We hereby certify that all the authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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