Molecular Carcinogenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma

Craig, Amanda Jean; Wang, Xin Wei

doi:10.1007/978-981-16-3615-8_6

753 Accesses

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Hepatitis B virus (HBV) is a major risk factor for the development of HCC. HBV oncogenic mechanisms are both indirect and direct. Indirectly, repetitive liver injury is induced by consistent inflammation and oxidative stress due to chronic infection of HBV. Over time this causes genomic instability, telomere shortening, and malignant transformation. The HBx protein encoded by HBV can also directly contribute to oncogenesis by deregulating the cell cycle, causing mitochondrial dysfunction and activating proliferation pathways. In addition, HBV genome integration also contributes to malignant transformation through both direct and indirect mechanisms. Random insertions lead to genomic instability. Insertional mutagenesis can also cause the constitutive activation of oncogenes such as TERT at the integration site. Particular characteristics of the HBV genome, including genotypes and mutations, have been reported to increase the risk of developing HCC. Comprehensive genomic profiling of hundreds of HBV-related HCC has determined recurrent alterations and integration sites. Molecular classification schema characterizes a majority of HBV-related HCC tumors as Proliferative and associated with a poorer prognosis. Prevention, including vaccination programs, remains the best method to decrease the incidence of HBV-related HCC. Promising immunotherapies specifically targeting HBV epitopes are being developed. In this chapter, we will review the current knowledge regarding the impact of HBV on development of HCC.

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Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Amanda Jean Craig & Xin Wei Wang
Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Xin Wei Wang

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Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
Jia-Horng Kao

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Craig, A.J., Wang, X.W. (2021). Molecular Carcinogenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma. In: Kao, JH. (eds) Hepatitis B Virus and Liver Disease. Springer, Singapore. https://doi.org/10.1007/978-981-16-3615-8_6

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