The partially doubled-stranded DNA is repaired to form a circular extra-chromosomal molecule called the covalently closed circular DNA
(cccDNA),  which is the transcriptional template for the viral messenger RNAs (mRNAs).
Transcription of hepatitis B virus covalently closed circular DNA
is regulated by cpg methylation during chronic infection.
Kao, "Persistence of hepatitis B virus covalently closed circular DNA
in hepatocytes: Molecular mechanisms and clinical significance," Emerging Microbes and Infections, vol.
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.
Viral eradication is not currently a goal of therapy, as none of the available therapeutic agents clear the highly stable covalently closed circular DNA
(cccDNA) from hepatocytes.
The rcDNA can be converted into a stable covalently closed circular DNA
(cccDNA) in the nucleus, after which it serves as the original template for viral replication and plays an important role in HBV persistence in the nucleus of infected hepatocytes (7), which may explain HBV reactivation and why HBV cannot be completely eliminated by antiviral agents (7, 8).