Role of microvesicles as markers of inflammation and adverse clinical outcomes in orthotopic liver transplantation

Microvesicles (MV) are intracellular transmitters that participate in both physiological and pathological conditions, such as inflammatory processes. During orthotopic liver transplantation (OLT), the abrupt exacerbation of inflammatory response contributes to adverse transplant outcomes. Our hypothesis is that MVs are released due to the OLT-associated inflammatory response and may serve as biomarkers of OLT short-term prognosis. In this context, the aim of this study was to evaluate changes in MV marker levels during OLT and their association with adverse outcomes. Blood samples of patients submitted to OLT were collected on three occasions: pretransplant, reperfusion phase and end of hospitalization. The following MVs markers were quantified by flow cytometry: CD41A+-MV, CD162+-MV, CD31+-MV, CD9+-MV and CD81+-MV. ANOVA with repeated measures, Spearman correlation and regression models were performed for data analysis. Ninety patients were included with a median age of 60 years; most of them had viral or alcoholic cirrhosis. The levels of all MV markers increased from the pretransplant to the liver reperfusion phase and returned to their basal levels before hospital discharge. During reperfusion, the levels of CD162+-MV (r 0.703; P = 0.034) were correlated with prothrombin time, and the levels of CD41A+-MV (r 0.220; P = 0.047) and CD81+-MV (r 0.332; P = 0.002) were correlated with serum lactate. Increased levels of MVs expressing CD162 (OR = 2.34; 95% CI 1.23 – 4.47; P = 0.01) and CD31 (OR = 2.00; 95% CI 1.01 – 3.99; P = 0.05) in the reperfusion phase were associated with an increased risk of death. Increased levels of CD162+-MV were also associated with the risk of infection during hospitalization (OR = 1.59; 95% CI 1.06 - 2.39; P = 0.03). Our results suggest that MV expressing platelet-endothelium and leukocyte-platelet adhesion antigens are released after ischemia‒reperfusion injury and are associated with the risk of infectious complications and death during OLT.