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Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation

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Xu, Jin ; Hassan-Ally, Mohammad ; Casas-Ferreira, Ana María ; Suvitaival, Tommi ; Ma, Yun ; Vilca-Melendez, Hector ; Rela, Mohamed ; Heaton, Nigel ; Wayel, Jassem ; Legido-Quigley, Cristina. / Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation. In: Journal of Clinical Medicine. 2020 ; Vol. 9, No. 3.

Bibtex

@article{2c491877f8de4a55a859187bc080fbc2,
title = "Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation",
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.",
author = "Jin Xu and Mohammad Hassan-Ally and Casas-Ferreira, {Ana Mar{\'i}a} and Tommi Suvitaival and Yun Ma and Hector Vilca-Melendez and Mohamed Rela and Nigel Heaton and Jassem Wayel and Cristina Legido-Quigley",
year = "2020",
month = "3",
day = "5",
doi = "10.3390/jcm9030711",
language = "English",
volume = "9",
journal = "Journal of Clinical Medicine",
issn = "2077-0383",
publisher = "M D P I AG",
number = "3",

}

RIS

TY - JOUR

T1 - Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation

AU - Xu, Jin

AU - Hassan-Ally, Mohammad

AU - Casas-Ferreira, Ana María

AU - Suvitaival, Tommi

AU - Ma, Yun

AU - Vilca-Melendez, Hector

AU - Rela, Mohamed

AU - Heaton, Nigel

AU - Wayel, Jassem

AU - Legido-Quigley, Cristina

PY - 2020/3/5

Y1 - 2020/3/5

N2 - 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.

AB - 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.

U2 - 10.3390/jcm9030711

DO - 10.3390/jcm9030711

M3 - Journal article

VL - 9

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

SN - 2077-0383

IS - 3

M1 - 117

ER -

ID: 59547675