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Glycome patterns of perfusate in livers before transplantation associate with primary non-function

(2018) GASTROENTEROLOGY. 154(5). p.1361-1368
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Abstract
BACKGROUND & AIMS: Primary 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. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: In 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.
Keywords
Liver Failure, Glycomics, Secretion, Hepatocyte, Glycan, Primary Nonfunction, HEPATOCELLULAR-CARCINOMA PATIENTS, EARLY ALLOGRAFT DYSFUNCTION, SERUM-PROTEIN GLYCOMICS, DONOR RISK INDEX, GRAFT FAILURE, N-GLYCOME, EXPERIENCE, VIABILITY, ISCHEMIA, RETRANSPLANTATION

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Chicago
Verhelst, Xavier, Anja Geerts, Ina Jochmans, Dieter Vanderschaeghe, Agnes Paradissis, Aude Vanlander, Frederik Berrevoet, et al. 2018. “Glycome Patterns of Perfusate in Livers Before Transplantation Associate with Primary Non-function.” Gastroenterology 154 (5): 1361–1368.
APA
Verhelst, X., Geerts, A., Jochmans, I., Vanderschaeghe, D., Paradissis, A., Vanlander, A., Berrevoet, F., et al. (2018). Glycome patterns of perfusate in livers before transplantation associate with primary non-function. GASTROENTEROLOGY, 154(5), 1361–1368.
Vancouver
1.
Verhelst X, Geerts A, Jochmans I, Vanderschaeghe D, Paradissis A, Vanlander A, et al. Glycome patterns of perfusate in livers before transplantation associate with primary non-function. GASTROENTEROLOGY. 2018;154(5):1361–8.
MLA
Verhelst, Xavier, Anja Geerts, Ina Jochmans, et al. “Glycome Patterns of Perfusate in Livers Before Transplantation Associate with Primary Non-function.” GASTROENTEROLOGY 154.5 (2018): 1361–1368. Print.
@article{8544691,
  abstract     = {BACKGROUND \& AIMS: Primary 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.
METHODS: We 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.
RESULTS: The 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 {\textlangle} .0001).
CONCLUSIONS: In 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.},
  author       = {Verhelst, Xavier and Geerts, Anja and Jochmans, Ina and Vanderschaeghe, Dieter and Paradissis, Agnes and Vanlander, Aude and Berrevoet, Frederik and Dahlqvuist, G{\'e}raldine and Nevens, Frederik and Pirenne, Jacques and Rogiers, Xavier and Callewaert, Nico and Troisi, Roberto and Van Vlierberghe, Hans},
  issn         = {0016-5085},
  journal      = {GASTROENTEROLOGY},
  keyword      = {Liver Failure,Glycomics,Secretion,Hepatocyte,Glycan,Primary Nonfunction,HEPATOCELLULAR-CARCINOMA PATIENTS,EARLY ALLOGRAFT DYSFUNCTION,SERUM-PROTEIN GLYCOMICS,DONOR RISK INDEX,GRAFT FAILURE,N-GLYCOME,EXPERIENCE,VIABILITY,ISCHEMIA,RETRANSPLANTATION},
  language     = {eng},
  number       = {5},
  pages        = {1361--1368},
  title        = {Glycome patterns of perfusate in livers before transplantation associate with primary non-function},
  url          = {http://dx.doi.org/10.1053/j.gastro.2017.12.027},
  volume       = {154},
  year         = {2018},
}

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