New aspects on reperfusion injury to liver -: impact of organ harvest

The aetiology of primary graft non-function and dysfunction is unknown but most likely involves Kupffer cell-dependent reperfusion injury; however, reasons for transplant failure are complex and involve organ retrieval, preservation and transplantation. Important factors include the donor's condition, cold and warm ischaemic times, operative complications in the recipient, the immune status of the recipient and surgical experience. The donor operation and surgical technique also have an effect on outcome after transplantation. This is important, since surgical organ manipulation of the liver during harvest cannot be prevented completely with standard procedures. This is especially true during organ harvest for living-donor liver transplantation and split-liver transplantation in general. Most recently, an experimental setting has conclusively demonstrated that gentle in situ organ manipulation by touching, retracting and moving liver lobes gently during harvest dramatically reduces survival after transplantation via Kupffer cell-dependent mechanisms. These mechanisms involve disturbances of hepatic microcirculation, a hypermetabolic state of the liver, hypoxia and almost complete denudation of endothelial lining cells. Glycine, a non-essential, nontoxic amino acid, which prevents activation of Kupffer cells, prevented all effects of harvest-related injury to the liver when given before transplantation. Based on these data, intravenous glycine has been administered to patients before reperfusion of their liver transplant. Both serum transaminases and the rate of primary non-function have been dramatically reduced, compared with historic controls. These preliminary clinical results with glycine before reperfusion are promising for further improvement of the overall outcome after liver transplantation.