Tissue Factor Expression on Blood Monocytes in Patients with Chronic Liver Disease

Abstract

Background: Chronic liver disease is a world wide common pathology characterized by an inflammatory and fibrotic process that may lead to progressive evolution from chronic hepatitis to cirrhosis. Monocyte play a crucial role in the pathogenesis of inflammation and fibrosis in chronic liver diseases. Tissue factor (TF) is one of the proteins that participate in haemostatic and inflammatory processes. Aim of the work: We aim to assess the expression of tissue factor on activated peripheral blood monocyte population in patients with HCV induced chronic liver disease in relation to the degree of hepatic insufficiency and haemostatic imbalance and its relevance in aggravating the acute attack of haematemesis in these patients. Subjects and Methods: This study was conducted on 60 patients classified according to Child Pugh classification to Child A (15 patients), B (15 patients), C (15 patients) and Child C during acute attack of hematemesis (15 patients), 15 healthy subjects served as normal controls. Immunophenotype characterization for identification of monocyte tissue factor expression (CD142) on activated blood monocyte population (CD11b and CD14) in different groups studied was carried out by flow cytometric analysis using monoclonal antibodies anti-CD142, -CD11b and -CD14, respectively. Results: Data demonstrated a significant increase in the expression of each of CD11b, CD14 and CD142 revealing increased expression of tissue factor on peripheral blood monocyte in different groups of patients compared to healthy subjects, especially cases during acute attack of haematemesis. Expression of CD11b, CD14 and CD142 on peripheral blood monocytes increased in step wise fashion in conjunction with worsening severity of liver disease as assessed by Child Pugh staging. Conclusion: Our data showed a progressive increase in monocyte tissue factor expression in patients with chronic liver disease which matched the perpetuation of liver cirrhosis. The interplay of several factors such as endotoxemia, lipopolysaccharides, oxidative stress and proinflammatory cytokines may be responsible for the increase in monocyte tissue factor expression leading to monocytes and platelet stimulation. The overexpression of monocyte tissue factor in patients with chronic hepatitis C virus may play a key role in the intensification of the inflammatory and immunological processes in conjunction with activation of the coagulation mechanisms. The interaction of all these phenomena may trigger bleeding by perturbing the unstable hemostasis in frail patients with chronic liver disease