Enhanced inflammatory cytokine production at ischemia/reperfusion in human liver resection.

Background/aims: Clinical implications of acute reactant cytokine responses remain to be clarified in the setting of ischemia/reperfusion of human liver during liver resection and transplantation.

Methodology: In serial samples of portal and systemic venous blood we examined acute inflammatory cytokine activities at the time points--before i), at the end of clamping ii), and one hour iii) and day 1 iv) after continuous hepatic inflow occlusion in 25 patients undergoing elective hepatectomy (15 major and 10 minor). Responses of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 were compared with intraoperative parameters such as the duration of hepatic inflow occlusion and portal venous pressure during the occlusion, postoperative hepatocyte injury markers such as serum transaminases and bilirubin and also related complications.

Results: Portal interleukin-6 levels were significantly elevated during hepatic inflow occlusion, as compared with the systemic events (P < 0.02, at time point ii), but there were no differences in the interleukin-8 levels between the portal and systemic circulation. The increase in portal interleukin-6 levels during liver resection (time points, ii and iii) significantly correlated with the duration of hepatic inflow occlusion (48 +/- 9 min, mean +/- SD), portal venous pressure (500 +/- 127 mmH2O), and postoperative serum levels of transaminases (day 1; S-ALT, 705 +/- 1023 U/L; S-AST 892 +/- 1255 U/L) and maximum bilirubin (2.6 +/- 2.5 mg/dL). Interleukin-8 levels in the portal circulation showed no such correlation, but the levels in systemic blood showed significant positive relationships with the intra- and postoperative parameters. One patient who died had an enhanced generation of the cytokines in the presence of an elevated portal venous pressure.

Conclusions: These observations suggest that overproduction of acute reactant cytokines (interleukin-6 from the portal system and interleukin-8 from the systemic circulation) in hepatic ischemia/reperfusion relates positively with postoperative hepatocyte injury in humans. We propose that hepatectomy done under a prolonged continuous inflow occlusion should be reconsidered when an enhanced generation of acute cytokines is anticipated, especially in case of a markedly high portal pressure during hepatic pedicle clamping.