Tissue Expression of TNF a and VEGF in Chronic Liver Disease and Hepatocellular Carcinoma

Aim and Background: The molecular mechanisms that lead to cancer in chronic inflammation and the role of angiogenesis in inflammation-associated cancer remain poorly understood. We measured levels of messenger RNA (mRNA) tran-scripts, mature protein for TNF-a and VEGF and serum TNF-a level to assess the possible implication of TNF-a-induced angiogenesis in providing a molecular link between inflam-mation and the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). Patients and Methods: Ninety patients were enrolled: 30 cases of CHC without cirrhosis, 28 cases of CHC with liver cirrhosis, and 32 cases of HCC and hepatitis C virus infection. Ten wedge liver biopsies, taken during laparoscopic cholecys tectomy, were served as normal controls. Serum TNF-a levels were measured using ELISA technique; TNF-a and VEGF proteins were detected in hepatic tissue by indirect Immuno-histochemical technique; In Situ Hybridization was performed for measurement of mRNA for TNF-a and VEGF. Results: The highest hepatic expression of TNF-a was noticed in LC specimens compared to non cirrhotic CHC and HCC. Hepatic expression of VEGF and serum level of TNF-a revealed significant increase with the progression of the disease and in cases with higher grades of inflammation or stages of fibrosis. Expression of mRNA of both TNF-a and VEGF shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positivity in cases that developed HCC. Conclusions: VEGF signaling could be one of the molecular signaling pathways involved in TNF-a induced angio-genesis which might pose an important link between inflam-mation and fibrosis in CHC and HCC development and progression. Moreover, serum inflammatory biomarkers can be used to monitor the disease progression.