O176: Complement inhibition enhances hepatocyte viability in a cell model of transplant ischaemia reperfusion injury

Abstract

Abstract Background Liver transplantation is limited by the number of optimal organs for transplantation. Ischaemia reperfusion injury (IRI) plays a key role in the utilisation of organs for transplantation - many organs are still not used due to concerns over viability. We evaluated the C5 inhibitor Eculizumab (EZB) in a cell model of IRI. Methods HepG2 cells, an immortalised hepatocyte cell-line, were utilised to model IRI. Cells were incubated in an anoxic chamber to model 'ischaemia' and then 'reperfused' in a normoxic incubator for 4 and 1 hours, respectively. The incubation media was supplemented with perfusate from donation after circulatory death (DCD) livers that had undergone standard normothermic machine perfusion (n=2) and EZB treated perfusate (n=2). Results The IRI model reduced cell viability and proliferation (p≤0.05). However, the model created no significant changes in the production of biomarkers VEGF, IL-10, IL-8, GDF-15 and ROS (p>0.05). Notably, EZB therapy significantly increased anti-inflammatory IL-10 production (p≤0.0001) and expression (p≤0.001), whilst enhancing cell viability and proliferation (p≤0.0001). Conclusion The complement system may play an important role within IRI and complement inhibition is a promising treatment for DCD livers, as demonstrated by treatment of cells with EZB therapy. Further work is required to optimise the models and treatment strategy before clinical testing.