New combination therapy offers chance of healing hepatitis B

The point of attack of their therapy is the viral HBx protein, which protects the cccDNA in the cell nucleus from silencing by preventing a host factor (SMC complex) from binding to it. The team treated the animals on the one hand with the antiviral cytokine interferon-alpha, which was already shown to reduce viral RNA, and on the other they suppressed the formation of the HBx protein by RNA interference, a method in which the translation from RNA to protein is inhibited. In both cases, they were able to abrogate HBx production in most infected cells, and thus to deactivate the cccDNA through reappearance of the host restriction factor. In addition, they combined this treatment with the administration of bulevirtide, able to prevent the entry of HBV into the cells and thus a reinfection. In this way, the effect of the cccDNA deactivation could be maintained even beyond the end of treatment. Bulevirtide, better known by the research name myrcludex, was co-developed in the DZIF and has recently been approved for the European market as an active substance in the treatment of hepatitis D.

"This combination therapy was able to achieve the sustained shutting down of the cccDNA in infected cells," Prof. Dandri explains. She directs the "HBV Cure" project in the DZIF and the "Virushepatitis" working group in the UKE. Even though it has as yet only been tested in the mouse model, Prof. Dandri is convinced of the combination: "The results show that the HBV genome can be shut down with certain combination treatments. These approaches can now be applied in clinical studies in order to achieve a functional cure of chronic hepatitis B."