Reperfusion Injury in Liver Allografts

Liver transplantation is increasingly used for treatment of end-stage liver disease and thousands of transplants are 

Unlike the liver injury that occurs with toxic chemicals (see above), reperfusion injury affects not only the hepatocytes but also the endothelial cells that line the sinusoids as an important primary target. It is thought that there may be some aspects of preservation-reperfusion injury that are unique to the liver and UW solution is apparently more effective in this tissue than in others (Clavien aal., 1992). The principle characteristic of this injury is that it involves damage to the sinusoidal cells such that leucocytes and platelets are stimulated to adhere on reperfusion. 

It is known that, while the injury is not manifest until reperfusion with oxygenated solution commences, the duration of the p eriod of preservation is the major determinant of the extent of the preservation-reperfusion injury. Hence, changes in the liver during the ischaemic period prepare the liver for injury when oxygen is reintroduced. The target of preventive measures should therefore be the ischaemic changes or the events that occur immediately after reperfusion. In the latter case, reactive oxygen free radicals may be involved. 

Under normal conditions the sinusoidal endothelial cells are flat thin cells lying close against the hepatocyte surface, separated only by the periplasmic space. Cold preservation of the liver causes the endothelial cells to round up and detach, although they are not actually 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

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Clavien, P. and Harvey, P.R.C. (1992). Preservation and reperfusion injuries in liver allografts. Transplantation 53, 957-978. 

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