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PLoS One. 2019 Jul 29;14(7):e0220376. doi: 10.1371/journal.pone.0220376. eCollection 2019.

Genomic modeling of hepatitis B virus integration frequency in the human genome.

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Gilead Sciences Inc., Foster City, CA, United States of America.


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.

Conflict of interest statement

O.P., G.W., B.D., R.R., A.G., M.S., Z.Y, and Z.J. are employees of Gilead Sciences and own Gilead stock. Gilead Sciences affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

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