TRANSHEPATIC METABOLISM OF TNF-α, IL-6, AND ENDOTOXIN IN THE EARLY HEPATIC REPERFUSION PERIOD AFTER HUMAN LIVER TRANSPLANTATION

Abstract

Several studies have shown that the postoperative course of cytokines such as TNF-α or IL-6 is predictive of rejection and infection after human orthotopic liver transplantation (OLT). The aim of this prospective clinical trial was to evaluate the impact of transhepatic metabolism of endotoxin (ET), tumor necrosis-factor-alpha (TNF-α), and interleukin-6 (IL-6) after hepatic ischemia/reperfusion on the postoperative graft function. In 13 consecutive elective adult OLT patients with primary grafts, we determined concentrations of ET, TNF-α, and IL-6 in the radial artery, portal vein, and right hepatic vein at 1, 4, 7, 10, and 13 min after reperfusion. Of the 13 patients, four had ET levels below the detection limit (<10 ng/L), and one patient had extremely high ET concentrations (151 ng/L in the hepatic vein). In the remaining patients the mean ET levels were 26pm14,26pm15, and 24pm14 ng/L in the portal vein, hepatic vein, and in the radial artery, respectively. These values indicate that in patients with a moderately elevated ET level, no transhepatic concentration differences of ET exist. However, in the patient with severe endotoxemia, the liver was apparently an ET-producing organ (HV-P: 29pm13 ng/L). TNF-α levels were not measurable in four patients, and varied between 15 and 72 pg/ml (portal vein) in the remaining patients. The transhepatic concentration differences (HV-P and HV-A, respectively) of patients with PNF or dysfunction were higher than in those with "good" or "excellent" graft function (HV-P: 160pm122 pg/ml vs. 7.3pm9.7 pg/ml; P<0.01 and HV-A: 137pm101 pg/ml vs. 3.9pm12 pg/ml; P<0.01, respectively). Arterial IL-6 levels were below 88 pg/ml (mean value: 31pm20 pg/ml) at the beginning of the operation, and increased considerably in three patients during the anhepatic phase and after reperfusion. No clinical correlation was found with the transhepatic concentration differences of IL-6. We conclude that in OLT patients without infection no transhepatic ET exchange was documented. However, a stimulated hepatic TNF-α release seems to be predictive of the beginning of liver dysfunction.