Sex difference in the tolerance of hepatic ischemia-reperfusion injury and hepatic estrogen receptor expression according to age and macrosteatosis in healthy living liver donors

BACKGROUND Hepatic estrogen signaling, which is important in liver injury/recovery, is determined by the level of systemic estrogen and hepatic estrogen receptor. We aimed to evaluate whether female's advantage in the tolerance of hepatic ischemia-reperfusion injury decreases according to the age of 40 y (systemic estrogen decrease) and macrosteatosis (hepatic estrogen receptor decrease). METHODS We included 358 living liver donors (128 females and 230 males). The tolerance of hepatic ischemia-reperfusion injury was determined by the slope of the linear regression line modeling the relationship between the duration of intraoperative hepatic ischemia and the peak postoperative transaminase level. Estrogen receptor content was measured in the biopsied liver samples using immunohistochemistry. RESULTS In the whole cohort, the regression slope for aspartate transaminase was comparable between females and males (P=0.940). Within the subgroup of ≤40 y donors, the regression slope was significantly smaller in females (P=0.031), whereas it was comparable within >40 y donors (P=0.867). Within the subgroup of ≤40 y non-macrosteatotic donors, the regression slope was significantly smaller in females in univariable (P=0.002) and multivariable analysis (P=0.006), whereas the sex difference was not found within ≤40 y macrosteatotic donors (P=0.685). Estrogen receptor content was significantly greater in females within ≤40 y non-macrosteatotic donors (P=0.021), whereas it was not different in others of >40 y or with macrosteatosis (P=0.450). CONCLUSIONS The tolerance of hepatic ischemia-reperfusion injury was greater in females than in males only when they were <40 y and without macrosteatosis. The results were in agreement with hepatic estrogen receptor immunohistochemistry study.