News & Views | Published:


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

Nature Reviews Gastroenterology & Hepatology volume 15, pages 195196 (2018) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  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.

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

  3. 3.

    & Molecular biology of hepatitis B virus infection. Virology 479–480, 672–686 (2015).

  4. 4.

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

  5. 5.

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

  6. 6.

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

  7. 7.

    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).

  8. 8.

    , & What is new on HBsAg and other diagnostic markers in HBV infection. Best Pract. Res. Clin. Gastroenterol. 31, 281–289 (2017).

  9. 9.

    et al. Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo. Gut (2017).

  10. 10.

    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).

Download references


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

Author information


  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover; the German Centre for Infection Research (DZIF), partner-site Hannover-Braunschweig; and the Centre for Individualised Infection Medicine (CIIM), Hannover, Germany.

    • Markus Cornberg
    •  & Michael P. Manns


  1. Search for Markus Cornberg in:

  2. Search for Michael P. Manns in:

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.

Corresponding authors

Correspondence to Markus Cornberg or Michael P. Manns.

About this article

Publication history



Further reading

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing