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Endotoxins, tumor necrosis factor-␣ (TNF-␣), interleukin-1 (IL-1), and IL-6 are believed to have a key role in liver transplantation. The origin and course of these factors is not completely known. In this prospective study of 40 patients, we sought more understanding of the relations between these factors and their effects on clinical outcome by sampling at different sites. Endotoxemia was only present in 20% of the patients. In 75% of these patients, it was present during the anhepatic phase and quickly resolved after reperfusion. Endotoxemia was not related to a clinical adverse event. TNF-␣ was released from the graft after reperfusion, and initial levels after reperfusion were related to predonation levels in the donor. Only levels of TNF-␣ in the recipient before transplantation were found to be predictive of postoperative complications. We conclude that monitoring endotoxins and these cytokines is of very limited value in predicting outcome. (Liver Transpl 2000;6:480-488.) L iver transplantation is standard treatment for patients with end-stage liver disease. Although improvements over the years have increased survival, initial liver function is not optimal in all cases, 1 and infection and rejection are common. Research has focused on graft preservation and reperfusion injury 2 as causative factors for these events. Reperfusion injury is characterized by a loss of endothelial cell viability associated with Kupffer cell activation. 3 Proinflammatory cytokines, especially tumor necrosis factor-␣ (TNF-␣), 4 are presumed to have a key role in this process. Elevated levels of cytokines have been reported after liver transplantation, as well as after other types of surgery. 5 The exact dynamics in cytokine concentrations are not clear. [6][7][8] Several factors may influence levels of cytokines, such as the presence of endotoxins during the liver transplantation procedure, 9 ischemia, and manipulation of other organs during transplantation, especially the splanchnic viscera. 10 Postreperfusion systemic levels of cytokines in the transplant recipient may be influenced by their serum levels in the donor. 11 Finally, preoperative systemic levels of cytokines in the transplant recipient might be an important factor because they are related to the nature and stage of the underlying disease. 12,13 The role of cytokines in human liver transplantation remains controversial. 6,14 There is some evidence that cytokines are involved in rejection and infection in the early postoperative phase, but available data are not consistent.We performed this study to evaluate changes in cytokine levels during and shortly after orthotopic liver transplantation and to assess their relation to clinical outcome. Patients and MethodsThe study was approved by the institutional review board of our hospital, and informed consent was obtained from each participating patient or a relative, in case of coma. Liver TransplantationDonor livers were not accepted when the donor was aged older than 65 years; had a history of liver disease, alcoholis...

Hyperthermic isolated limb perfusion with recombinant TNF-alpha leads to high systemic concentrations of TNF-alpha, probably due to leakage of recombinant TNF-alpha from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-alpha, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients.

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SDD leads to the additional costs of SDD medication and routine cultures, whereas no savings in other costs and no improvement in infection episodes are realised. Consequently, SDD may be considered as a nonefficient approach in patients undergoing liver transplantation. The additional costs of severe infection are considerable.

The hypothesis that in humans, TNF-alpha induces vasodilation and shock through activation of inducible nitric-oxide synthase and subsequent formation of excessive quantities of nitric oxide is not substantiated by our results. Normal nitric oxide metabolite concentrations were found in the presence of high TNF-alpha concentrations and shock. Other mechanisms that do not involve the nitric oxide pathway are likely to play a role in the generation of hypotension and septic shock in this setting.

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