Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: Donor shortage motivated alternative practices including living donor liver transplantation (LTx). This study aimed to identify molecular profiles and characteristics in living donor versus deceased donor grafts.
Methods: This study included 59 consecutively transplanted liver grafts from living (LDLT, n = 10), deceased heart-beating (DBD, n = 44), and donor after cardiac death (DCD, n = 5). DBDs were also grouped depending on cold-ischemia time as more or less 8 hours. Tissue biopsy samples were collected previous implantation (back bench). Total RNA was isolated, labeled, and used for gene expression microarrays hybridization. GeneChip microarray analyses were performed using Affymetrix Expression and Transcriptome Analysis consoles. Probeset summaries were obtained using RMA algorithm. Pairwise comparisons were fit using two-sample t-test. Probesets with p-values <0.001 under controlled FDR <10% and ±2.0 fold-change was considered significant. Gene ontology and molecular pathways analyses were performed using Ingenuity Pathway Analysis tool.
Results: Demographic and clinical characteristics were similar among study groups. Pairwise comparison analyses revealed no significant differentially expressed genes among DBDs grouped by CIT or between DCDs and DBDs. LDLT vs. DBDs pairwise comparison identified 455 significantly differentially expressed genes. Ontology and molecular pathways analysis predicted positive activation of proliferation mechanisms in hepatocytes and apoptosis inhibition in LDLTs. More interestingly, LDLTs molecular profiles compared to DBDs evidenced upregulation of genes favoring lipid/fatty acid and xenobiotic/drug metabolisms. Top canonical pathways include LPS/IL1 mediated inhibition of RXR function, NRF2-mediated oxidative stress response (NRF2-MOSR), PXR/RXR activation, Nicotine degradation III, and bupropion degradation as most relevant. Coincidently, most significant toxic functional pathways involved oxidative stress, NRF2-MOSR, upregulation of cytochrome P-450 panel (xenobiotic), CAR/RXR activation, and upregulation of genes involved in liver proliferation.
Conclusions: Molecular profiles in living donor liver allografts suggest activation of proliferation mechanisms in hepatocytes and apoptosis inhibition with maintenance of hepatic functions and homeostasis.
To cite this abstract in AMA style:Gehrau R, Suh J, Brayman K, Rasmussen S, Dumur C, Mas V, Maluf D. Liver Allografts from Living Donors Demonstrate High Expression of Hepatic Functional Genes Compared With Deceased Donors [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/liver-allografts-from-living-donors-demonstrate-high-expression-of-hepatic-functional-genes-compared-with-deceased-donors/. Accessed April 7, 2020.
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