Dataset Information

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.

SUBMITTER: Xu J

PROVIDER: S-EPMC7141328 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Xu Jin J Hassan-Ally Mohammad M Casas-Ferreira Ana María AM Suvitaival Tommi T Ma Yun Y Vilca-Melendez Hector H Rela Mohamed M Heaton Nigel N Wayel Jassem J Legido-Quigley Cristina C

Journal of clinical medicine 20200305 3

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 (<i>n</i> = 24) and donation after ...[more]

PMID: 32151072

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Project description:BackgroundThe reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.MethodsRecipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.ResultsEarly reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9-99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).ConclusionsObserved graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.

Dataset Information

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

Publications

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

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