Conceptual models for the initiation of hepatitis B virus-associated hepatocellular carcinoma.
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.
['Tu|Thomas|T|', 'Budzinska|Magdalena A|MA|', 'Shackel|Nicholas A|NA|', 'Jilbert|Allison R|AR|']
D000818:Animals D005075:Biological Evolution D014408:Biomarkers, Tumor D006528:Carcinoma, Hepatocellular 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 D019694:Hepatitis B, Chronic D006801:Humans D008113:Liver Neoplasms D008954:Models, Biological D009154:Mutation D059016:Tumor Microenvironment D014779:Virus Replication
hepatocellular carcinoma hepatitis B virus evolution of hepatocyte subpopulations clonal expansion of hepatocytes