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

Abstract

Recent studies show that extracellular vesicles (EVs) are present throughout the organism, usually in body fluids, and are intracellular signal transmitters under physiological and pathological conditions. They are cell particles which detached from their cell of origin, and carry the same surface receptors that its parent, enabling its travel and action anywhere in the body. Your actions occur mainly in inflammatory processes, thromboses, degenerative diseases, and cancer. The formation of these vesicles is part of the immunological mechanisms and mayincrease or inhibit the immune response, and carry pathogen antigens to antigen presenting cells. In orthotopic liver transplantation (OLT) there is a state persistent inflammatory disease determined by several parameters, such as the clinical conditions of patients, conditions of the transplanted organ and blood component transfusion during thetransplant. The more exacerbated the inflammation process the greater the risk ofgraft and patient mortality. The pathophysiological mechanisms behind the process inflammation associated with OLT are not elucidated. The association between EVs and inflammation post liver transplantation has not been investigated in clinical studies to date. Thus, The aim of this study is to evaluate the association between TOF and EVs formation in patients undergoing this treatment. For this, patients undergoing TOF will be consecutivelyincluded in the study for 2 years. Patients will be followed from pre-transplantimmediate to discharge, death or retransplantation. Blood samples will be taken in the pre transplant at the end of surgery and at the end of follow-up. Will be quantified in these samples of the following EVs markers: CD14 (monocyte marker), CD41a (platelet marker), CD45 (leukocyte marker), CD62P (P-selectin marker), CD162 (P-selectin binding glycoprotein-1 or PSGL-1 marker) and CD31 (endothelial-platelet adhesion). Variations in the levels of these markers in the 3collection times will be evaluated by analysis of variance (ANOVA) with repeated measurements.Afterwards, we will evaluate the possible determinants associated with EVs circulating levels over end of the surgical period by linear regression methods. Predetermined determinants: age, gender, MELD score, body mass index, diagnosis of hepatocellular carcinoma, ischemia times and transfusion volume during surgery. Finally, we will evaluate the association between EVs levels atend of the surgical period and the occurrence of adverse outcomes (prolonged hospitalization,graft and death) by logistic regression methods. EVs evaluation as markers of liver transplant inflammation may contribute to the health of these early identification of the risk of post transplant complications.