BACKGROUND: Preservation induced injury is a major contributing factor to early graft dysfunction in liver allograft recipients. We hypothesized that changes in gene expression represent the earliest indicator of ischemia/reperfusion-related injuries measurable in the graft and could be used as prognostic marker for the occurrence of graft-related complications. METHODS: We studied the expression of 67 genes, known to play a role in acute inflammatory processes by real-time polymerase chain reaction in 59 postperfusion biopsies. The level of expression was correlated with the occurrence of graft-related complications. RESULTS: We identified six genes that were significantly correlated with the occurrence of early graft dysfunction (Spearman test, two-tailed; P<0.05). High C-reactive protein (CRP) gene expression levels correlated significantly with the need of therapeutic interventions due to graft-related complications (P=0,011). Furthermore, five genes related to vascular endothelial cell physiology (CTGF, WWP2, CD274, VEGF. and its receptor FLT1) showed significantly reduced expression in the postperfusion biopsies of patients with need of therapeutic interventions due to graft-related complications in the first month (P<0.05). Using a risk score based on the expression of these five genes, complications could be predicted with 96% sensitivity (ROC analysis, specificity: 74%, positive predictive value: 72%, negative predictive value: 96%). CONCLUSION: Quantitative gene expression analysis in postperfusion biopsies may be a valuable tool to prospectively identify patients at risk for early clinical allograft dysfunction after liver transplantation.
BACKGROUND: Preservation induced injury is a major contributing factor to early graft dysfunction in liver allograft recipients. We hypothesized that changes in gene expression represent the earliest indicator of ischemia/reperfusion-related injuries measurable in the graft and could be used as prognostic marker for the occurrence of graft-related complications. METHODS: We studied the expression of 67 genes, known to play a role in acute inflammatory processes by real-time polymerase chain reaction in 59 postperfusion biopsies. The level of expression was correlated with the occurrence of graft-related complications. RESULTS: We identified six genes that were significantly correlated with the occurrence of early graft dysfunction (Spearman test, two-tailed; P<0.05). High C-reactive protein (CRP) gene expression levels correlated significantly with the need of therapeutic interventions due to graft-related complications (P=0,011). Furthermore, five genes related to vascular endothelial cell physiology (CTGF, WWP2, CD274, VEGF. and its receptor FLT1) showed significantly reduced expression in the postperfusion biopsies of patients with need of therapeutic interventions due to graft-related complications in the first month (P<0.05). Using a risk score based on the expression of these five genes, complications could be predicted with 96% sensitivity (ROC analysis, specificity: 74%, positive predictive value: 72%, negative predictive value: 96%). CONCLUSION: Quantitative gene expression analysis in postperfusion biopsies may be a valuable tool to prospectively identify patients at risk for early clinical allograft dysfunction after liver transplantation.
Authors: Kojiro Nakamura; Min Zhang; Shoichi Kageyama; Bibo Ke; Takehiro Fujii; Rebecca A Sosa; Elaine F Reed; Nakul Datta; Ali Zarrinpar; Ronald W Busuttil; Jesus A Araujo; Jerzy W Kupiec-Weglinski Journal: J Hepatol Date: 2017-08-23 Impact factor: 25.083
Authors: Kojiro Nakamura; Shoichi Kageyama; Shi Yue; Jing Huang; Takehiro Fujii; Bibo Ke; Rebecca A Sosa; Elaine F Reed; Nakul Datta; Ali Zarrinpar; Ronald W Busuttil; Jerzy W Kupiec-Weglinski Journal: Am J Transplant Date: 2017-12-18 Impact factor: 8.086
Authors: Shoichi Kageyama; Kojiro Nakamura; Takehiro Fujii; Bibo Ke; Rebecca A Sosa; Elaine F Reed; Nakul Datta; Ali Zarrinpar; Ronald W Busuttil; Jerzy W Kupiec-Weglinski Journal: Hepatology Date: 2018-05-10 Impact factor: 17.425
Authors: Wenyu Xiang; Shuai Han; Cuili Wang; Hongjun Chen; Lingling Shen; Tingting Zhu; Kai Wang; Wenjie Wei; Jing Qin; Nelli Shushakova; Song Rong; Hermann Haller; Hong Jiang; Jianghua Chen Journal: Front Med (Lausanne) Date: 2022-01-07
Authors: Philipp Houben; Ralph Hohenberger; Kenya Yamanaka; Markus W Büchler; Peter Schemmer Journal: Ann Transplant Date: 2018-07-13 Impact factor: 1.530