Ischaemia-reperfusion injury of the liver: treatment in theory and in practice

Cold ischaemia-reperfusion injuries are an unavoidable feature of current liver transplantation procedures. Damage to liver grafts accures mainly from hypothermic storage under hypoxic conditions (cold ischaemia), from sustained ischaemia during implantation into the recipient (rewarming ischaemia) and from restoration of blood and oxygen to the graft (reperfusion injury). These three stages are characterized by progressive deteriorations in hepatic function, with sinusoidal endothelial cells most affected during cold ischaemia. Activation of Kupffer cells (hepatic macrophages) at reperfusion augments damage to both endothelial and parenchymal cells by the release of numerous compounds which initiate and perpetrate injury and impair the hepatic microcirculation. The key events in the expression of ischaemia-reperfusion injury are detailed and therapeutic interventions are described which target these steps. The treatments discussed include University of Wisconsin (UW) preservation solution, calcium channel blockade, inhibitors of Kupffer cell activation, promoters of microvascular vasodilation, hepatoprotectants and the use of anti-oxidants.