O95: The role of the complement system in mediating ischaemic cholangiopathy in DCD liver transplantation

Abstract Background The discrepancy between available organs and the number of patients on the waiting list have led to an increasing number of donor after circulatory death (DCD) liver grafts being used. DCD liver grafts suffer from a higher risk of ischaemic cholangiopathy, the pathophysiology of which is poorly understood. We hypothesized that the complement system mediates damage to the arterial endothelium, thereby affecting the ability of cholangiocytes to regenerate. Methods Livers declined for clinical transplantation were perfused for up to 10 hours with anti-coagulated packed red cells at 37° with or without complement inhibition. Levels of circulating complement components, tissue binding of complement proteins, and organ damage markers were measured. Results 5 DBD and 5 DCD livers were perfused, and 5 further DCD livers being perfused with eculizumab. C3 production was significantly higher in the untreated DCD cohort compared to DBD livers at 10 hours (52.68 mg/ml vs 8.62 mg/ml, p<0.005). C5b-9 deposition on the arterial endothelium of the portal tracts was significantly higher in the untreated DCD cohort compared to the treated DCD livers (mean 0.9 R.U vs 0.4 R.U, p<0.05). There was a non-significant difference in bile production and composition between the treated DCD and untreated DCD cohort. Conclusions There is evidence that the complement system mediates the damage to the arterial endothelium within the portal tracts of the liver. This damage could be ameliorated by complement inhibition. Further work to correlate this findings with clinical outcomes will be required.