BACKGROUND & AIMS: Ischemic-type biliary lesions (ITBL) are the second most common cause of graft loss after liver transplantation. Though the exact pathophysiology of ITBL is unknown, bile duct injury during graft preservation is considered to be a major cause. Here we investigated whether the release of cholangiocyte-derived microRNAs (CDmiRs) during graft preservation is predictive of the development of ITBL after liver transplantation. METHODS: Graft preservation solutions (perfusates) and paired liver biopsies collected at the end of cold ischemia were analysed by RT-qPCR for CDmiR-30e, CDmiR-222, and CDmiR-296 and hepatocyte-derived miRNAs (HDmiRs) HDmiR-122 and HDmiR-148a. MicroRNAs in perfusates were evaluated on their stability by incubation and fractionation experiments. MicroRNA profiles in perfusates from grafts that developed ITBL (n=20) and grafts without biliary strictures (n=37) were compared. RESULTS: MicroRNAs in perfusates were proven to be stable and protected against degradation by interacting proteins. Ratios between HDmiRs/CDmiRs were significantly higher in perfusates obtained from grafts that developed ITBL (p<0.01) and were identified as an independent risk factor by multivariate analysis (p<0.01, HR: 6.89). The discriminative power of HDmiRs/CDmiRs in perfusates was validated by analysis of separate brain death- (DBD) and cardiac death donors (DBD; p ≤ 0.016) and was superior to expression in liver biopsies (C=0.77 in perfusates vs. C<0.50 in biopsies). CONCLUSIONS: This study demonstrates that differential release of CDmiRs during graft preservation is predictive of the development of ITBL after liver transplantation. This provides new evidence for the link between graft-related bile duct injury and the risk for later development of ITBL.
BACKGROUND & AIMS:Ischemic-type biliary lesions (ITBL) are the second most common cause of graft loss after liver transplantation. Though the exact pathophysiology of ITBL is unknown, bile duct injury during graft preservation is considered to be a major cause. Here we investigated whether the release of cholangiocyte-derived microRNAs (CDmiRs) during graft preservation is predictive of the development of ITBL after liver transplantation. METHODS: Graft preservation solutions (perfusates) and paired liver biopsies collected at the end of cold ischemia were analysed by RT-qPCR for CDmiR-30e, CDmiR-222, and CDmiR-296 and hepatocyte-derived miRNAs (HDmiRs) HDmiR-122 and HDmiR-148a. MicroRNAs in perfusates were evaluated on their stability by incubation and fractionation experiments. MicroRNA profiles in perfusates from grafts that developed ITBL (n=20) and grafts without biliary strictures (n=37) were compared. RESULTS: MicroRNAs in perfusates were proven to be stable and protected against degradation by interacting proteins. Ratios between HDmiRs/CDmiRs were significantly higher in perfusates obtained from grafts that developed ITBL (p<0.01) and were identified as an independent risk factor by multivariate analysis (p<0.01, HR: 6.89). The discriminative power of HDmiRs/CDmiRs in perfusates was validated by analysis of separate brain death- (DBD) and cardiac death donors (DBD; p ≤ 0.016) and was superior to expression in liver biopsies (C=0.77 in perfusates vs. C<0.50 in biopsies). CONCLUSIONS: This study demonstrates that differential release of CDmiRs during graft preservation is predictive of the development of ITBL after liver transplantation. This provides new evidence for the link between graft-related bile duct injury and the risk for later development of ITBL.
Authors: Shaojun Shi; Eliano Bonaccorsi-Riani; Ivo Schurink; Thierry van den Bosch; Michael Doukas; Karishma A Lila; Henk P Roest; Daela Xhema; Pierre Gianello; Jeroen de Jonge; Monique M A Verstegen; Luc J W van der Laan Journal: Front Immunol Date: 2022-05-17 Impact factor: 8.786
Authors: Bote G Bruinsma; Wilson Wu; Sinan Ozer; Adam Farmer; James F Markmann; Heidi Yeh; Korkut Uygun Journal: PLoS One Date: 2015-03-30 Impact factor: 3.240
Authors: Gerd Otto; Michael Heise; Jochen Thies; Michael Pitton; Jens Schneider; Gernot Kaiser; Peter Neuhaus; Otto Kollmar; Michael Barthels; Josef Geks; Wolf Otto Bechstein; Achim Hellinger; Jürgen Klempnauer; Winfried Padberg; Nils Frühauf; Andre Ebbing; Dietmar Mauer; Astrid Schneider; Robert Kwiecien; Kai Kronfeld Journal: Transplant Direct Date: 2017-06-26
Authors: Ming Zhou; Hidetaka Hara; Yifan Dai; Lisha Mou; David K C Cooper; Changyou Wu; Zhiming Cai Journal: Int J Mol Sci Date: 2016-08-01 Impact factor: 5.923
Authors: Alix P M Matton; Jasmijn W Selten; Henk P Roest; Jeroen de Jonge; Jan N M IJzermans; Vincent E de Meijer; Robert J Porte; Luc J W van der Laan Journal: Clin Transplant Date: 2020-02-20 Impact factor: 2.863