The effect of the neutrophil elastase inhibitor sivelestat on early injury after liver resection.

The effects of sivelestat on endotoxin-induced lung injury, postperfusion lung injury, and ischemia-reperfusion are known, yet the benefits of sivelestat during liver surgery have yet to be elucidated. The aim of the present study was to assess the effects of sivelestat, with a focus on postoperative chemical data, in hepatectomized patients. A prospective clinical study was conducted in 50 patients undergoing hepatic resection. Patients were randomly assigned to receive Elaspol, sivelestat (ELP group, n = 25) or placebo (control group, n = 25). Perioperative blood chemistry values in both groups, including high-mobility group box 1 (HMGB1) and interleukin (IL)-6, were monitored. The HMGB1 levels increased immediately after the operation (from the intraoperative period to the second postoperative day [POD]) in the control group. Compared to the control group, the levels of HMGB1 in the ELP group were significantly suppressed by the perioperative administration of sivelestat. At POD 1, the levels of IL-6 in the ELP group decreased more rapidly than those before the operation compared to the control group. A human clinical study demonstrated the effect of polymorphonuclear leukocyte elastase inhibitor on the earliest markers of liver injury. The present study showed that patients who received sivelestat had reduced release of HMGB1, and that IL-6 levels decreased more rapidly in patients treated with sivelestat than in those who received the placebo. The most appropriate dose, timing, and duration of sivelestat in humans remain unclear; however, it may have therapeutic potential for various liver injuries.