Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

Abstract

Hepatitis C virus (HCV) infection is a major public health problem all over the world. Egypt has the highest prevalence of HCV worldwide (17-26%) with subsequent high morbidity from chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). Matrix metalloproteinase are proteolytic enzymes that play a role in the degradation of extracellular matrix (ECM) which is necessary for invasion and metastasis of tumor cells. The present work was designed to study the relationship between HCV infection and circulating MMP-2 level in chronic HCV patients (either without or with hepatic complication) and compared to that of non-HCV cirrhotic patients as well as healthy controls, in order to clarify the role of HCV in changing microenvironment and underlying mechanisms associated with dissemination of malignancy. The level of MMP-2 was estimated in sera collected at different stages of HCV infections as well as in ascetic fluids collected from those developing either HCC or cirrhosis. Statistical analysis of their results revealed that MMP-2 levels were significantly elevated in all patient groups as compared to healthy controls. The level of MMP-2 in HCV patients with HCC was significantly elevated when compared to other HCV patients. Meanwhile MMP-2 in ascetic fluids of cirrhotic patients were similar to that detected in their sera, while in HCC patients there were 2.4 times elevations in serum level of MMP-2 as compared to that in ascetic fluids. These results revealed that HCV infection is not only responsible for biochemical and hematological abnormalities recorded at chronic stages of infection but also creating a microenvironmental change by enhancing MMP-2 release, which effect on infected cell by obliging them to modify their phenotype in order to survive, thus increasing the invasion potential and facilitate tumor progression.