BackgroundWe have previously demonstrated lactate release by the liver itself in hepatectomies performed under selective hepatic vascular exclusion. We hypothesized that ischemic preconditioning applied in this setting might lead to a reduction of hepatic lactate production. MethodsTwenty-one patients underwent hepatectomy under inflow and outflow occlusion combined with ischemic preconditioning (IP group, n = 21). These patients were matched 1:1 with patients subjected to the same technique of hepatectomy under vascular occlusion without ischemic preconditioning (control group, n = 21). The transhepatic lactate gradient (hepatic vein–portal vein) was calculated before liver dissection and 60 min post-reperfusion. ResultsIn the control group, the transhepatic lactate gradient before liver resection was negative indicating consumption by the liver. After 60 min post-reperfusion, this gradient became positive, indicating net lactate production by the liver (0.2±0.3 vs. −0.3±0.2 mmol/L, P < 0.001). In the IP group, the liver consumed lactate both before resection and 60 min post-reperfusion (gradients −0.2±1.1 and −0.1±0.6 mmol/L, respectively). The magnitude of lactate release by the liver correlated with systemic hyperlactatemia post-reperfusion and 24 h postoperatively (r2 = 0.54, P < 0.001 and r2 = 0.67, P < 0.001, respectively). Significant correlations between the transhepatic lactate gradient post-reperfusion and peak postoperative AST as well as the apoptotic response of the liver remnant were also demonstrated (r2 = 0.72, P < 0.001 and r2 = 0.66, P < 0.001, respectively). ConclusionThe microcirculatory derangement and cellular aerobic metabolism breakdown elicited by ischemia–reperfusion insults can be prevented with hepatoprotective measures such as ischemic preconditioning. The transhepatic lactate gradient could act as a monitoring and prognostic tool of the efficacy of ischemic preconditioning.