Gut: Combined therapy helps treat HBV

February 6, 2021 // -- Currently, about 260 million people (more than 3% of the global population) are chronically infected with HBV;
at the German Centre for Infection Research (DZIF) and the University Hospital of Eppendorf (UKE) have now developed a new combination therapy that has been shown to be very effective in their infection models.
(Photo: www.pixabay.com) the new treatment is based on shutting down the viral hepatitis B genome located in the nucleus of an infected liver cell.
infected liver cells, the viral genome is transformed into closed ring DNA molecules in the nucleus.
this DNA is a stable molecule called co-priced closed ring DNA (cccDNA) and used as a template for the production of new viruses.
cccDNA represents a central repository of the hepatitis B virus and makes it sustainable in the liver.
virologist Dr Maura Dandri and his team at UKE managed to prevent HBV-cccDNA from producing other viruses in animal models.
the attack point of their therapy is the virus HBx protein, which protects cccDNA from silence in the nucleus by blocking the binding of host factors (SMC complexes).
the team treated animals with antiviral cytokine IFN-α, which has been shown to reduce viral RNA, and inhibited the formation of HBx proteins through RNA interference.
both cases, they eliminate HBx production in most infected cells, in which cccDNA is insulates through the re-emergence of host limiting factors.
, they used the treatment in a joint way with bulevirtide to prevent HBV from entering the cells and thus prevent re-infection.
, the effect of cccDNA indation can be maintained even after treatment.
Dandri explained: "This combination therapy enables the continuous closure of cccDNA in infected cells.
dandri believes in the effectiveness of this treatment, even if it is only tested in mouse models: "The results show that the HBV genome can be shut down with certain combination therapies.
these methods can now be used in clinical studies to cure chronic hepatitis B.
" () Source: New combination therapy offers chance of healing hepatitis B Original source: Lena Allweiss et al, Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the virus in vivo, Gut (2021). DOI: 10.1136/gutjnl-2020-322571