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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)371-380
Number of pages10
JournalTransplantation
Volume103
Issue number2
DOIs
Publication statusAccepted/In press - Jun 7 2018

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Natural Killer Cells
Liver Transplantation
Liver
Brain
Transplants
Brain Death
Biopsy
Operative Time
Proportional Hazards Models
Allografts
Flow Cytometry
Regression Analysis
Phenotype
Sensitivity and Specificity

ASJC Scopus subject areas

  • Transplantation

Cite this

@article{fa53d9c1824e43ff8a3e1ae6ea0599ac,
title = "Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation: A Time-to-Rejection Analysis",
abstract = "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.",
author = "Duilio Pagano and Ester Badami and Conaldi, {Pier Giulio} and Aurelio Seidita and Fabio Tuzzolino and Marco Barb{\`a}ra and {di Francesco}, Fabrizio and Alessandro Tropea and Rosa Liotta and Gaia Chiarello and Angelo Luca and Salvatore Gruttadauria",
year = "2018",
month = "6",
day = "7",
doi = "10.1097/TP.0000000000002322",
language = "English",
volume = "103",
pages = "371--380",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation

T2 - A Time-to-Rejection Analysis

AU - Pagano, Duilio

AU - Badami, Ester

AU - Conaldi, Pier Giulio

AU - Seidita, Aurelio

AU - Tuzzolino, Fabio

AU - Barbàra, Marco

AU - di Francesco, Fabrizio

AU - Tropea, Alessandro

AU - Liotta, Rosa

AU - Chiarello, Gaia

AU - Luca, Angelo

AU - Gruttadauria, Salvatore

PY - 2018/6/7

Y1 - 2018/6/7

N2 - 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.

AB - 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.

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U2 - 10.1097/TP.0000000000002322

DO - 10.1097/TP.0000000000002322

M3 - Article

C2 - 29912045

AN - SCOPUS:85059308756

VL - 103

SP - 371

EP - 380

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 2

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