Cyclooxygenase-2 (COX-2) Gene Expression in Peripheral Blood as Non Invasive Predictor of HCV Disease Progression

Cyclooxygenase-2 (COX-2) is one of mediators of inflammation and angiogenesis. COX-2 is involved in immune response suppression, apoptosis inhibition, regulation of angiogenesis and tumor cell invasion. The COX-2 gene overexpression have recently been shown to be associated with several human cancers but their association with chronic hepatitis C (CHC) and hepatocarcinogenesis has yet to be investigated. To elucidate whether COX-2 is involved in progression of CHC to liver cirrhosis and HCC development, we attempted to examine COX-2 mRNA in peripheral blood of CHC patients with and without cirrhosis and to compare with patients with hepatocellular carcinoma (HCC) and healthy controls. Seventy four patients having HCV-related liver pathology were included in the current study, 26 patients having CHC without cirrhosis, 22 having CHC with cirrhosis (LC) and 28 having proved HCC. In addition, 20 healthy volunteers were included as a control group. Clinical examination and radiological examinations were done, liver function tests, HCV antibody and HCV-RNA were done. Prostaglandin E2 (PGE2) by immunoassay and quantitative real time PCR for COX-2 gene were performed. A significant increase in the COX-2 mRNA expression was detected in CHC, LC and HCC cases as compared to controls and its level was significantly higher in HCC cases followed by LC then cases of CHC. The COX-2 expression was positively correlated with PGE2 serum level, the biological inflammatory markers of the liver (serum levels of aminotransferases, alkaline phosphatase, bilirubin levels), markers of disease progression (serum albumin, prothrombin concentration, AFP) and stage of liver fibrosis. Conclusions: The overproduction of COX-2 in peripheral blood is associated with progressive liver disease in patients with CHC and contributes to HCC development in cirrhosis. This suggests that the use of selective COX-2 inhibitors in association with antiviral therapy, might be useful as antifibrotic drugs in chronic HCV infection and provide a potential preventive measure for cirrhosis and malignant transformation.