Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

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. 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: We aim 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. Results: Data demonstrated a significant increase in the circulating levels of GM-CSF, TGF- Ý and Ü-SMA, along with a significant increased expression of CXCR4 in conjunction with a significant increase 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. Data also revealed that the expression of CD34, CD45, collagen type I and CXCR4 positive fibrocytes, in peripheral blood, increased in step wise fashion in conjunction with worsening severity of liver disease. Conclusion: Our data showed a progressive increase of circulating fibrocytes in peripheral blood in patients with chronic liver disease which matched the advancement of the disease and the intensification of liver fibrosis. Liver fibrosis is associated with increased levels of circulating TGF-Ý1 and lipopolysaccharide, activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen Type I. TGF-Ý 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

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