No cure for hepatitis B and D without targeting integrated viral DNA?

RNA interference (RNAi) is a novel concept to target transcripts derived from HBV covalently closed circular DNA. The study by Wooddell et al. investigates the RNAi-based therapy ARC-520 in patients and chimpanzees with chronic HBV infection and uncovers HBV DNA integration as a crucial source of hepatitis B surface antigen, which has not been considered in current strategies to accomplish HBV cure.

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Figure 1: Schematic illustration of how ARC-520 targets HBV.


  1. 1

    European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol. 67, 370–398 (2017).

  2. 2

    Bock, C. T. et al. Structural organization of the hepatitis B virus minichromosome. J. Mol. Biol. 307, 183–196 (2001).

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Seeger, C. & Mason, W. S. Molecular biology of hepatitis B virus infection. Virology 479–480, 672–686 (2015).

    Article  PubMed  Google Scholar 

  4. 4

    Cornberg, M. et al. The role of quantitative hepatitis B surface antigen revisited. J. Hepatol. 66, 398–411 (2017).

    CAS  Article  PubMed  Google Scholar 

  5. 5

    Testoni, B., Durantel, D. & Zoulim, F. Novel targets for hepatitis B virus therapy. Liver Int. 37 (Suppl. 1), 33–39 (2017).

    CAS  Article  PubMed  Google Scholar 

  6. 6

    Bertoletti, A. & Ferrari, C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut 61, 1754–1764 (2012).

    CAS  Article  PubMed  Google Scholar 

  7. 7

    Wooddell, C. I. et al. RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg. Sci. Transl Med. 9, eaan0241 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    Höner zu Siederdissen, C., Maasoumy, B. & Cornberg, M. What is new on HBsAg and other diagnostic markers in HBV infection. Best Pract. Res. Clin. Gastroenterol. 31, 281–289 (2017).

    Article  PubMed  Google Scholar 

  9. 9

    Allweiss, L. et al. Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo. Gut https://doi.org/10.1136/gutjnl-2016-312162 (2017).

    Article  PubMed  Google Scholar 

  10. 10

    Bogomolov, P. et al. Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: first results of a phase Ib/IIa study. J. Hepatol. 65, 490–498 (2016).

    CAS  Article  PubMed  Google Scholar 

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The authors thank F. Rinker for drafting the figure and T. Bock for critical review of the manuscript.

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Correspondence to Markus Cornberg or Michael P. Manns.

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Competing interests

M.C. received payments for lectures and consultation from Bristol-Myers Squibb, Gilead Sciences and Roche. M.M. received payments for lectures, consultation and trial support from Bristol-Myers Squibb, CureVac, Gilead Sciences, Glaxo Smith Kline, MSD, Novartis and Roche.

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Cornberg, M., Manns, M. No cure for hepatitis B and D without targeting integrated viral DNA?. Nat Rev Gastroenterol Hepatol 15, 195–196 (2018). https://doi.org/10.1038/nrgastro.2017.185

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