Chronic hepatitis B: New insights into Peg-IFNα therapy

21 November 2013
A chronic hepatitis B virus (HBV) infection may result – as a continuous process of inflammation – to cirrhosis and hepatocellular carcinoma. Treatment with pegylated interferon α (Peg-IFNα) is one therapy option. The substance supports the immune system in its fight against the virus. In their recent publication “Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon-alpha administration” the research group of Professor Maura Dandri has now presented new findings on the underlying mechanisms of Peg-IFNα antiviral effects. The studies were realized with financial support from German Research Foundation (CRC 841) and from Hoffmann-La Roche. The researchers could show that Peg-IFNα can trigger significant declines in HBV antigen levels – and this without the help of immune cell responses of the infected organism. It seems that Peg-IFNα treatment of human hepatocytes first inhibits the activity of the viral mini chromosome (covalently closed circular DNA, cccDNA) that plays a central role in the complex replication cycle of the virus. The cccDNA serves as a highly efficient matrix for the continuous production of new virus antigens and is found within the nucleus of infected liver cells. For a long time, it was considered to be inaccessible from therapeutic point of view and responsible for the fact that the hepatitis B virus is able to persist in the host organism. The present study, however, highlights the potential of agents which can silence or even destabilize the virus cccDNA.

Bibliography:
Allweiss L., Volz T., Lütgehetmann M., Giersch K., Bornscheuer T., Lohse A.W., Petersen J., Ma H., Klumpp K., Fletcher S.P., Dandri M. (2013). Immune cell responses are not required to induce substantial hepatitis B virus antigen decline during pegylated interferon alpha administration. J. Hepatology (in press).

For further information about the SFB 841 project A5 “Molecular mechanisms of hepatitis B virus persistence in chronically infected uPA chimera mice” see here.

Further related SFB 841 publications:
Belloni L, Allweiss L, Guerrieri F, Pediconi N, Volz T, Pollicino T, Petersen J, Raimondo G, Dandri M, Levrero M. (2012). IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest. 122(2):529-37.