Role of Circulating Hematopoietic Fibrocytes in Chronic Hepatitis C Patients Induced Liver Fibrosis

Abstract

Background: Bone marrow derived fibrocytes may play an important role in pathogenesis and resolution of liver fibrosis. These cells may offer new approaches for better understanding the pathogenesis of liver fibrosis.
 Aim of the work: To define the proportion of circulating fibrocytes with hematopoietic progenitor origin as defined by CD45 and CD34 positivity and to assess whether they are increased in patients with chronic C hepatitis in correlation to the degree of liver fibrosis.
 Subjects and Methods: Sixty HCV patients were classified according to METAVIR score into 4 stages of liver fibrosis, 15 age and sex-matched controls were included. Flowcytometric analysis for circulating levels of fibrocytes CD34+ve cells, CD45+ve cells, collagen type I+ve cells and CXCR4+ve cells was carried out using monoclonal antibodies (anti-CD34, CD45, collagen type I and CD184). GM-CSF, TGF-β and α-SMA were assessed using ELISA.
 Results and Conclusions: A significant increase in the circulating levels of GM-CSF, TGF- β and α-SMA, with a significant increase in the percentage of cells express CXCR4and in the co expression of CD34, CD45 and collagen type I positive cells in different groups of patients compared to control group, denoting the presence of an increased proportion of circulating fibrocytes in peripheral blood of these patients. The percentage of fibrocytes that positively expression CD34, CD45, collagen type I and CXCR4, were increased in step wise fashion in conjunction with worsening severity of liver disease.
 Liver fibrosis is associated with increased levels of circulating TGF-β1 and lipopolysaccharide, activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen Type I. TGF-β and LPS play a critical role in fibrogenesis and trigger fibrocyte recruitment to the injured liver promoting their differentiation into collagen type I producing myofibroblast, supporting that fibrocytes may become a novel target for anti fibrotic therapy.