Abstract
Hepatitis B infection is a world-wide public health burden causing serious liver complications. Previous studies suggest that hepatitis B integration into the human genome plays a crucial role in triggering oncogenic process and may also constitutively produce viral antigens. Despite the progress in HBV biology and sequencing technology, our fundamental understanding of how many hepatocytes in the liver actually carry viral integrations is still lacking. Herein we provide evidence that the HBV virus integrates with a lower-bound frequency of 0.84 per diploid genome in hepatitis B positive hepatocellular cancer patients. Moreover, we calculate that integrated viral DNA generates ~80% of the HBsAg transcripts in these patients. These results underscore the need to re-evaluate the clinical end-point and treatment strategies for chronic hepatitis B patients.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Algorithms
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / virology*
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Endpoint Determination
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Gene Expression Profiling
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Gene Expression Regulation
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Genome, Human
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Hepatitis B / genetics*
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Hepatitis B / virology
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Hepatitis B Surface Antigens / genetics
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Hepatitis B virus / physiology*
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / virology*
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Virus Integration
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Whole Genome Sequencing
Substances
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Hepatitis B Surface Antigens
Grants and funding
This research was supported by Gilead Sciences. The funder provided support in the form of salaries for authors O.P., G.W., B.D., R.R., A.G., M.S., Z.Y, and Z.J, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.