Article

Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma

Department of Biology and Sbarro Health Research Organization, College of Science and Technology, Temple University, 1900 N. 12th Street, Philadelphia, Pennsylvania 19122, USA.
Nature Reviews Cancer (Impact Factor: 29.54). 12/2012; 13(2):123-35. DOI: 10.1038/nrc3449
Source: PubMed

ABSTRACT Hepatocellular carcinoma (HCC) is a highly lethal cancer, with increasing worldwide incidence, that is mainly associated with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections. There are few effective treatments partly because the cell- and molecular-based mechanisms that contribute to the pathogenesis of this tumour type are poorly understood. This Review outlines pathogenic mechanisms that seem to be common to both viruses and which suggest innovative approaches to the prevention and treatment of HCC.

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Available from: Mark A Feitelson, Jul 26, 2015
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    • "The putative mechanisms of how antiviral therapy reduces HCC risk may include downregulation of hepatic inflammation and related nuclear signaling pathways that lead to neoplastic transformation at the cellular level, as well as reversal of fibrosis and reduction of regenerative stimuli at the tissue level. Antiviral therapy may also reduce expression of HBx protein to levels insufficient to promote HCC development, or act at a genomic level by preventing HBV DNA integration into host chromosomes or affecting its malignant potential [3] [4] [5]. "
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    Journal of Hepatology 01/2015; 62(4). DOI:10.1016/j.jhep.2015.01.002 · 10.40 Impact Factor
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    • "Furthermore , one of the HBV-derived proteins, HBxAg, also has direct tumorigenic effects [155]. Hepatocyte regeneration, either influenced by KC or not, allows HBxAg integration in DNA of hepatocytes , which is one of the processes involved in the development of HCC (reviewed in [153]). Whether HBxAg directly interacts with KC is not described. "
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    ABSTRACT: Globally, over 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV). These chronic infections cause liver inflammation, and may result in fibrosis/cirrhosis or hepatocellular carcinoma. Albeit that HBV and HCV differ in various aspects, clearance, persistence and immunopathology of either infection depends on the interplay between the innate and adaptive responses in the liver. Kupffer cells, the liver-resident macrophages, are abundantly present in the sinusoids of the liver. These cells have been shown to be crucial players to maintain homeostasis, but also contribute to pathology. However, it is important to note that especially during pathology, Kupffer cells are difficult to distinguish from infiltrating monocytes/macrophages and other myeloid cells. In this review we discuss our current understanding of Kupffer cells, and assess their role in the regulation of anti-viral immunity and disease pathogenesis during HBV and HCV infection.
    Journal of Hepatology 05/2014; DOI:10.1016/j.jhep.2014.04.026 · 10.40 Impact Factor
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    • "hepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma (Arzumanyan et al., 2013). "
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