Immunohistochemical Study of TNFα, CD41 and PDGFR-β in Chronic Hepatitis C Patients Demonstrating the Relationship of Intrahepatic Platelet Accumulation to Thrombocytopenia and Hepatic Fibrosis

Abstract

Background: Chronic liver diseases (CLDs) are characterized by persistent liver injury and fibrosis, which are basic features that lead to liver cirrhosis and liver cell failure. Thrombocytopenia is a frequent complication of CLDs. The mechanisms of thrombocytopenia in CLD and cirrhosis are still unclear. Objective: The aim of the present work was to study intrahepatic expression of tumor necrosis factor alpha (TNFα), cluster of differentiation antigen 41 (CD41) and platelet-derived growth factor receptor beta (PDGFRβ) in patients with chronic hepatitis C (CHC) and their relation to the grade and stage of CHC. Also, we want to investigate the relationship between intrahepatic platelets (PLTs) and thrombocytopenia in CHC. Patients and Methods: Analytical cross-sectional study was conducted on fifty patients with proven CHC who were admitted to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. All patients were clinically examined and fully investigated. Liver biopsy was obtained for histopathological examination and immunohistochemical study using monoclonal antibodies against TNFα, CD41 and PDGFR-β. Results: Fifty patients were included, their age ranged from 20-59 years with a mean of 44.42±11.17 years. Forty patients (80%) were males and 10 (20%) were females. The mean average weighted scores (AWS) of imunohistochemical expression of TNFα, CD41 and PDGFR-β were significantly higher in grades 3&4
compared to lower grades (P<0.0001; 0.009; 0.05 respectively), in patients with fibrosis stage 3 versus earlier stages (P<0.0001; 0.001;
<0.04 respectively), and in thrombocytopenic group compared to non-thrombocytopenic group (P<0.001 for each). There was a significant negative correlation between peripheral PLT count and the AWS of TNFα, CD41, and PDGFR-β expression in CHC patients (r= - 0.37; P= 0.008 & r= -0.41; P= 0.007 & r= -0.34, P= 0.045 respectively). Conclusion: Expression of TNFα, CD41 and PDGFR-β markers was associated with progression of disease activity and fibrosis. Intrahepatic PLT accumulation in CHC may be involved in
thrombocytopenia and liver fibrosis.