
MOLECULAR PATHOGENESIS OF
HEPATOCELLULAR CARCINOMA Metodieva SN *Corresponding Author: Corresponding Author: S. Nikolova Metodieva, Department of Medical Genetics, Medical
Faculty, Medical University Sofia, 2 Zdrave str., 1413, Sofia, Bulgaria; Tel/Fax: + 359-2-9520-357;
E-mail: svetlana.metodieva@ yahoo.com page: 15
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INTRODUCTION
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. It ranks third in mortality rate and is responsible for approximately 600,000 to 1,000,000 deaths annually [1]. Hepatocellular carcinoma typically develops in close association with pre-existing cirrhosis. The liver with cirrhosis may contain pre-neo plastic lesions that are in an intermediate stage between non neoplastic regenerating nodules and malignant HCC. These nodular lesions are designated as dysplastic nodules and are further divided into low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs), depending on their histological examination. Progression of HCC proceeds from LGDNs and HGDNs to advanced HCC [2].
Hepatocellular carcinomas show a wide variability in incidence and in principal risk factors in different regions. Globally, chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) and prolonged dietary exposure to aflatoxin are responsible for about 80% of all HCC in humans [3]. It is most frequent in Eastern and South eastern Asia and sub-Saharan Africa, regions of high dietary aflatoxin exposure and endemic HBV infection. Recently, HCC has become more common in Japan and the United States in parallel with an increasing incidence of HCV and HBV infections leading to the development of chronic active hepatitis. In Northern Europe and the United States it is often related to alcoholic liver disease [1]. In areas with an intermediate incidence such as South ern Europe, HCV infection is considered to be the predom inant cause [3].
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