The role of graft manipulation in the mechanism of primary non-function in liver transplantation: cytokines and transcription factors

摘要

Graft manipulation Primary non-function and dysfunction occur in 5-30% of liver transplantation cases, resulting either in the need for retransplantation or in the death of the recipient. Since liver transplantation is the therapy of choice in an increasing number of liver diseases, and the organ pool is limited, there is an urgent need to understand the underlying mechanisms responsible for failure of transplanted livers. There are three crucial periods which can influence graft viability before rejection: harvest, cold storage and reperfusion. It has been demonstrated that reperfusion injury, rather than ischaemic cell damage developing during cold storage, predominates. This conclusion is based on the fact that after long cold storage in UW solution, reperfusion injury is minimized by Carolina Rinse solution. Injury from ischaemic cold storage alone would have sufficient time to develop, but does not become apparent. Several mechanisms, i.e. production of free radicals, disturbances of the microcirculation and activation of the coagulation system, are probably involved in mechanisms of reperfusion injury. In addition, several cell types are involved, e.g. migration and activation of leucocytes and damage to endothelial cells. Further, Kupffer cells, the resident macrophages in the liver, are activated upon reperfusion, causing them to release toxic mediators such as superoxide radicals, tumour necrosis factor (TNF) and arachidonic acid derivatives.