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Multicenter Study
Glycome Patterns of Perfusate in Livers Before Transplantation Associate With Primary Nonfunction.
- Xavier Verhelst, Anja Geerts, Ina Jochmans, Dieter Vanderschaeghe, Agnes Paradissis, Aude Vanlander, Frederik Berrevoet, Géraldine Dahlqvist, Frederik Nevens, Jacques Pirenne, Xavier Rogiers, Nico Callewaert, Roberto I Troisi, and Hans Van Vlierberghe.
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium; Laboratory of Hepatology Research, Ghent University, Ghent, Belgium.
- Gastroenterology. 2018 Apr 1; 154 (5): 1361-1368.
Background & AimsPrimary nonfunction (PNF) is a rare complication after liver transplantation that requires urgent retransplantation. PNF is associated with livers from extended criteria donors. Clinical and biochemical factors have not been identified that reliably associate with graft function after liver transplantation. Serum patterns of N-glycans associate with changes in the liver. We analyzed perfusate from grafted liver to identify protein glycosylation patterns associated with PNF.MethodsWe performed a prospective study of consecutive patients who underwent liver transplantation (66 patients, from 1 center, in the derivation set, and 56 patients, from 2 centers, in the validation set) in Belgium, from October 1, 2011, through April 30, 2017. All donor grafts were transported using cold static storage, and perfusate samples were collected from the livers by flushing of hepatic veins before transplantation. Protein-linked N-glycans were isolated from perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer. We compared glycan patterns between patients with vs without PNF of transplanted livers. PNF was defined as the need for urgent retransplantation when a graft had no evidence of function, after exclusion of other causes, such as hepatic artery thrombosis or acute cellular rejection.ResultsThe relative abundance of a single glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan (NGA2F) was significantly increased in perfusate of livers given to 4 patients who developed PNF after liver transplantation compared with livers given to patients who did not develop PNF. Level of NGA2F identified patients with PNF with 100% accuracy. This glycomarker was the only factor associated with PNF in multivariate analysis in the derivation and the validation sets (P < .0001).ConclusionsIn an analysis of patients who underwent liver transplantation, we associated graft perfusate level of glycan NGA2F present on perfusate proteins with development of PNF with 100% accuracy, and validated this finding in a separate cohort of patients. This biomarker might be used to assess grafts before transplantation, especially when high-risk organs are under consideration.Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
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