Analysis of transcriptomic changes during cold ischaemia in time-zero biopsies of liver allografts

• Published in: Zeitschrift für Gastroenterologie
• Main Authors: Lautem, A, Maass, T, Krupp, M, Rey, J, Itzel, T, Marquardt, J, Thorgeirsson, SS, Galle, PR, Barreiros, AP, Otto, G, Teufel, A
• Format: Conference Proceeding
• Language: English; German
• Published: 11.05.2016
• ISSN: 0044-2771; 1439-7803
• DOI: 10.1055/s-0036-1582065

Background: Liver transplantation remains the only treatment option for many patients with end-stage liver disease or acute liver failure. Despite substantial progress in preventing graft failure over the past decades, a substantial number of patents still suffer from progressive graft dysfunction, subsequently leading to re-transplantation or death. Thus identifying the molecular causes of graft failure would certainly be a major step ahead in organ preservation and patient survival. Cold ischemia time appears to be a good predictor among the factors influencing patient and graft survival. Meta-analysis have recently suggested increasing graft failures in patients receiving organs with cold ischemia time of more than 8 – 9 hours. Thus, identifying the molecular changes in grafts with more than 8 hours of cold ischemia may eventually aid to better preserve organs and help to further decrease graft failure. Methods: In order to identify early molecular changes in liver grafts associated with subsequent graft failure we collected time zero biopsies after liver reperfusion from 93 consecutive patients. Extensive transcriptomic profiling was performed using the gene expression microarrays. Results: Supervised analysis of molecular changes associated with increasing cold ischemia time included major networks associated with major changes in Inflammation, cell death and lipid metabolism. IL1, IL8, and IL32 were identified as key molecules associated with increased cold ischemia time. All three molecules showed an average increase throughout the time course of increasing cold ischemia. No overlap was seen compared to murine models of ischemia/reperfusion injury. Conclusion: transcriptomic profiling of time zero biopsies in patients with liver transplantation demonstrated enrichment of Inflammation, cell death and lipid metabolism with Il1, IL8, and IL32 being key members of the associated networks. A better understanding of their role during cold ischemia may aid better organ preservation strategies in the future.