Arrowhead Data Reveal Important Considerations for Future Hepatitis B Treatment
- Results May Guide New Clinical Approaches, Science Translational Medicine Study Shows -
In many patients, integrated HBV DNA appeared to be the dominant source of HBsAg production. The findings expand the understanding of HBV biology and host interactions, and could have important implications for future trial design and endpoint expectations for new therapies developed to cure chronic HBV. These data from study, "RNAi-based treatment of chronically infected patients and chimpanzees implicates integrated hepatitis B virus DNA as a source of HBsAg" were published in Science Translational Medicine.
The paper entitled, "RNAi-based treatment of chronically infected
patients and chimpanzees implicates integrated hepatitis B virus DNA as
a source of HBsAg," by
In the publication, several independent lines of evidence demonstrate that HBsAg is expressed not only from the episomal covalently closed circular DNA (cccDNA) minichromosome, but also from transcripts arising from HBV DNA integrated into the host genome. The latter was a large source of HBsAg production in HBeAg negative chimpanzees and presumed, by extension, in HBeAg negative and NUC experienced patients.
"This is an important finding with wide-reaching implications for the
field because production of viral proteins was previously thought to
depend only on transcription of viral cccDNA. We now understand that
integrated HBV DNA is a means of producing circulating HBsAg that is not
dependent on viral replication, which may contribute to sustained
suppression of the immune system and allow for continued virion
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