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N-glycan levels in liver grafts predict primary nonfunction after transplantation

NGA2F glycan levels present on perfusate proteins of liver grafts correlated with the development of primary nonfunction in patients who underwent liver transplantation, according to recently published data.

“A particular problem associated with the use of ... low-quality grafts is primary nonfunction (PNF),” Xavier Verhelst, MD, PhD, from the Ghent University Hospital in Belgium, and colleagues wrote. “The results of the present study ... provide a strong proof of concept that the analysis of N-glycans in preservation fluid can predict the appearance of PNF after liver transplantation.”

Verhelst and colleagues based the technique for N-glycan analysis on a DNA sequencer-assisted fluorophore-assisted capillary electrophoresis previously validated for serum analysis and urine analysis. They applied the technique on perfusate from patients who underwent liver transplantation.

The study comprised 66 liver transplantations performed in 64 patients and 56 patients as a validation cohort. From their samples, the researchers quantified 13 peaks that were detectable in all samples, then normalized their abundance to the total peak height intensity of each patient.

The perfusate N-glycan profile of patients with PNF was highly discriminative from patients without PNF based on the increased abundance of core-alpha-1,6-fucosylated biantennary structure (NGA2F) — an agalacto found in peak 1 — compared with patients with early allograft dysfunction (P < .0001) with an accuracy of 100% at a cut-off of 13%.

Multivariate analysis including NGA2F as a marker, donor risk index, and levels of aspartate aminotransferase and alanine aminotransferase in perfusate, showed that NGA2F independently predicted PNF. (P < .0001).

“The proposed glycomarker for PNF prediction managed to identify the four patients who developed PNF after liver transplantation by an analysis that could be performed before the liver transplantation, without false positives,” the researchers wrote. “This biomarker could be a tool to safely select high-risk organs (eg, [extended criteria donor] organs) for liver transplantation that otherwise would be discarded from the donor pool based on a conventional clinical assessment as it is often performed now.” – by Talitha Bennett

Disclosure: Verhelst reports he is listed as a co-inventor on the biomarker’s patent. Please see the full study for the other authors’ relevant financial disclosures.