RESUMO
Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.
RESUMO
Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.
RESUMO
Yellow fever (YF) is an infectious and acute viral haemorrhagic disease that triggers a cascade of host immune responses. We investigated the Th17 cytokine profile in the liver tissue of patients with fatal YF. Liver tissue samples were collected from 26 deceased patients, including 21 YF-positive and 5 flavivirus-negative patients, with preserved hepatic parenchyma architecture, who died of other causes. Histopathological and immunohistochemical analysis were performed on the liver samples to evaluate the Th17 profiles (ROR-γ, STAT3, IL-6, TGF-ß, IL-17A, and IL-23). Substantial differences were found in the expression levels of these markers between the patients with fatal YF and controls. A predominant expression of Th17 cytokine markers was observed in the midzonal region of the YF cases, the most affected area in the liver acinus, compared with the controls. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory cell infiltrates, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis. Hence, Th17 cytokines play a pivotal role in the immunopathogenesis of YF and contribute markedly to triggering cell damage in patients with fatal disease outcomes.