title: Conceptual models for the initiation of hepatitis B virus-associated hepatocellular carcinoma.
abstract: Although chronic hepatitis B virus (HBV) infection is a known risk factor for the development of hepatocellular carcinoma (HCC), the steps involved in the progression from normal liver to HCC are poorly understood. In this review, we apply five conceptual models, previously proposed by Vineis et al. to explain carcinogenesis in general, to explore the possible steps involved in the initiation and evolution of HBV-associated HCC. Available data suggest that the most suitable and inclusive model is based on evolution of hepatocyte subpopulations. In this evolutionary model, HCC-associated changes are driven by selection and subsequent clonal expansion of phenotypically altered hepatocyte subpopulations in the microenvironment of the HBV-infected liver. This model can incorporate the wide range of mechanisms proposed to play a role in the initiation of HCC including oncogenic HBV proteins, integration of HBV DNA and chronic inflammation of the liver. The model may assist in the early prevention, detection and treatment of HCC and may guide future studies of the initiation of HBV-associated HCC.
authors: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.|Liver Cell Biology, Centenary Institute, Sydney, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors: Thomas
authors: T
authors: Tu
authors: Liver Cell Biology, Centenary Institute, Sydney, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors: Magdalena A
authors: MA
authors: Budzinska
authors: Liver Cell Biology, Centenary Institute, Sydney, NSW, Australia.|Sydney Medical School, University of Sydney, Sydney, NSW, Australia.|A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors: Nicholas A
authors: NA
authors: Shackel
authors: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
authors: Allison R
authors: AR
authors: Jilbert
mesh_terms: D000818:Animals; D005075:Biological Evolution; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002472:Cell Transformation, Viral; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D020022:Genetic Predisposition to Disease; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008954:Models, Biological; D009154:Mutation; D059016:Tumor Microenvironment; D014779:Virus Replication
chemical_list: D014408:Biomarkers, Tumor
keywords: clonal expansion of hepatocytes; evolution of hepatocyte subpopulations; hepatitis B virus; hepatocellular carcinoma