Avaliação da expressão imuno-histoquímica do fator inibidor da migração de macrófagos e sua relação com a lesão de isquemia-reperfusão e eventos adversos pós transplante hepático

Abstract

Primary graft dysfunction is one of the most feared complications following liver transplantation, being associated with poorer graft and patient outcomes, prolonged length of hospital stay and an increase in transplantation costs. Ischemia reperfusion injury (IRI) is thought to be the pathological event behind primary graft dysfunction, and is the result of graft procurement and preservation. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine with glucocorticoid counter regulatory activity which is constitutively expressed in inflammatory cells, endothelial cells and epithelial cells. MIF has been studied in many inflammatory and autoimmune diseases, cancer, allograft rejection and, recently, in IRI in liver allografts. The aim of this study was to investigate MIF expression in post-reperfusion biopsies from human liver allografts and correlate with presence and severity of IRI and with clinical perioperative data. 103 liver allograft post-reperfusion biopsies from patients who underwent liver transplantation between 2000 and 2020 at Hospital das Clínicas from Federal University of Minas Gerais were reviewed and categorized regarding the presence and severity of IRI and steatosis and submitted to single immunostaining to MIF (ab65869). MIF immunohistochemical expression was quantified by applying the IHC Profiler plugin on the ImageJ Fiji software on the digitized slides. Medical records from the patients were revised to collect perioperative and clinical data. The histopathological assessment of IRI severity was as follows: no IRI (N = 49 biopsies, 47.6%), mild IRI (N = 24, 23.3%), moderate IRI (N = 25, 24.3%), severe IRI (N = 5, 4.9%). Most biopsies did not have significant steatosis (N = 91, 88.3%), while 10 biopsies (9.7%) presented mild steatosis, 1 (1.0%) had moderate and 1 (1%) had severe steatosis. MIF expression was categorized as low positive in 64 cases (62.1%), positive in 34 cases (33.0%) and negative in 5 cases (4.9%). MIF positive expression was correlated with no IRI or mild IRI on the histological assessment ((P = 0.01, OR: 1.259, 95% CI 1.058-1.499). None of the studied variables was associated with retransplantation or death within 15 days of the transplant. Our findings suggest that moderate to severe IRI is related to a rapid MIF release into the circulation, which results in a weaker intensity of the immunostain on the tissue. To further clarify MIF's role in IRI, we believe that more studies are warranted comparing MIF expression in the hepatocytes, biliary epithelium and immune cells, as well as measuring MIF serum and effluent concentrations.