Abstract
The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q < 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q < 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.
Highlights
There is an increasing need for organ transplantation, but the number of organs available remains insufficient [1,2]. This is reflected by the number of people registered in the Organ Donor Register (ODR) in the UK, which decreased from 2018 to 2019 [3], while in the same period, the number of patients on the active transplant list increased by 20%, reaching the number of 432 [3]
There were no significant differences between DBD and donation after circulatory death (DCD) groups in age, early allograft dysfunction (EAD)/early graft function (EGF), liver enzyme levels, hepatic steatosis or serum bilirubin levels
From the 12 selected features, 5 metabolites werFeivanenfeoatatuterdes(Twaebrle Sid2e).ntified as purines at pre-transplant, and their levels in DBD and DCD were represFenivteedfeaatsubreasr wpleortesidinenFtiigfiuedreaSs3p.uAridnedsitaitopnrael-ltyr,ajnitstperlaendt,sacnadttethrpeilroltesvreelspirnesDeBnDtinagndthDeCrDatiwoseroef the lerveeplrseosefnftoeudrapsubrairnpelsottsoitnhFoisgeuoref Su3r.aAted,dililtuiosntaralltye,djititnerFedigsucraett1er, pwloetrserepplorettseednt.inAgttthheeraptrioe-storafnthseplant stalegvee,lsthoefrfaotuiorspAuMrinPe/surtoatteh, oasdeenofosuirnaet/eu, rialltues,taradteendinine/Fuirgauterean1,dwheyrpeopxlaontttehdin. eA/ut rthateepwree-rterasnigspnliafinctantly hisgtahgeer,inththee rDaBtioDs grAoMupP/cuormatep,araeddetnoosthinee/DuCraDte,onaed(eqn
Summary
There is an increasing need for organ transplantation, but the number of organs available remains insufficient [1,2] This is reflected by the number of people registered in the Organ Donor Register (ODR) in the UK, which decreased from 2018 to 2019 [3], while in the same period, the number of patients on the active transplant list increased by 20%, reaching the number of 432 [3]. Optimal donors’ parameters in the case of donation after circulatory death (DCD) include age (
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