Molecular Mechanisms of Hepatitis B Virus-associated Hepatocellular Carcinoma

doi:2007.13.3.320

Korean J Hepatol > Volume 13(3); 2007 > Article

The Korean Journal of Hepatology 2007;13(3): 320-340.
doi: https://doi.org/10.3350/kjhep.2007.13.3.320

Molecular Mechanisms of Hepatitis B Virus-associated Hepatocellular Carcinoma

Neung Hwa Park, M.D., Young-Hwa Chung, M.D.1

Department of Internal Medicine, University of Ulsan College of Medicine, Biomedical Research Center, Ulsan University Hospital, Ulsan; Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center1, Seoul; Korea

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis. (Korean J Hepatol 2007;13:320-340)

KeyWords: Carcinoma, hepatocellular; Hepatitis B virus; Hepatitis B x protein (HBx); Transactivator