Epigenetic regulation of transcription could potentially disrupt transcription from cccDNA
contains methylationprone CpG islands  and thus epigenetic silencing of cccDNA
transcription may be possible.
Reisinger et al., "Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA
," Science, vol.
COPY NUMBERS OF HBV cccDNA
CORRELATED WITH CHILDPUGH SCORE AND SERUM AFP CONCENTRATIONS
Thus, detection of cccDNA
and viral RNA in liver tissue of baboon 9732 showed that HBV was replicating.
The level of hepatitis B core-related antigen (HBcrAg) in the serum, which is associated with the level of intrahepatic cccDNA
, was described as predicting a sustained response (14).
HBsAg responses observed with ARO-HBV are consistent with the ability of ARO-HBV to silence HBV mRNA from cccDNA
and host-integrated viral DNA, a major source of HBsAg in certain patient populations (Wooddell, 2018)
A total of 15,760,000 individuals corresponding to approximately one third of the adult population showed an encounter with HBV, indicating that these individuals carry covalently closed circular DNA (cccDNA
) of the virus in their liver.
INF helps eliminate the infected cells by reducing cccDNA
, while NAs' function is to elongate DNA which leads to the inhibition of HBV replication
However, the challenge of antiviral therapy is to clear the HBV covalently closed circular DNA (cccDNA
A more ambitious (but less likely) goal for some patients is loss of HBV surface antigen (HBsAg), appearance of HBV surface antibody (anti-HBs), HBV DNA negative, and silencing or eliminating cccDNA
(covalently closed circular DNA), a DNA structure that arises during the propagation of some viruses in the cell nucleus and remains there permanently with all current therapies and even with natural HBsAg clearance.
HBsAg is the most important serological marker of HBV infection, and serum HBsAg level correlates with the intrahepatic amount and transcriptional activity of covalently closed circular DNA (cccDNA
), the main replicative template of HBV.[sup] HBsAg loss and seroconversion to anti-HBs is generally considered to be the ultimate goal of therapy, indicating a complete response to treatment and the resolution of the disease.
Inside the nucleus, covalently closed circular DNA (cccDNA
) is converted from rcDNA and serves as a template for viral replication through RNA intermediates using reverse transcriptase.