How could we clear the cccDNA in liver cell?

I know anti-viral drug can reduce the cccDNA, but can not clear them all. That is why after long time antivirus therapy treatment, when you HBVDNA negtive and HBeAg - and HBeAb +, you can still chance to get relapse.
Adevofir 5 yrs treatment, 1/3 people relapse after stop Adv.
Enticavir will have less resisitance like adv.
More new drug like TDF,ETC,etc.

New research told us that HBsAg has some relationship with cccDNA, so doc use HBsAg quantitive measurement as a benchmark for the efficacy of anti-viral treatment. Like new drugs, NTZ, REP 9AC, etc....

So my question is if we can get the HBsAg lower to a undetectable level, is it means cccDNA is eradicated at all. How can we tell when it is the final point?

[stef2011]

is it means cccDNA is eradicated at all.

no it takes 10-15years to eradicate all cccdna but that's not important because hbsag is used by virus to suppress immune system, once hbsag is negative you develop hbsab antibodies which blocks viral entry, so when you get hbsag negative and hbsab>10miu/ml your immune system has total control of hbv infection and clears the virus like all other acute hbv cases seroconverters

so the point is hbsag makes hbv cronic (chronic), if you make it negative you clear it, at the moment only nitazoxanide, interferon (only those with low hbsag) and simvastatin (no data available) lower hbsag on hbe negative hbv

[Taj82]

Dear stef ....Sky's Qt still remains there.....

So my question is if we can get the HBsAg lower to a undetectable level, is it means cccDNA is eradicated at all. How can we tell when it is the final point?


How we can correlate HBsAg and ccDNA?

[studyforhope]

The presentation by Dr. Brunetto from Pisa, that stefano has recently posted shows you the correlation between HBsAg and cccDNA levels.

The formula for the quant HbSAg is:

Total amount of cccDNA copies
times transcriptional activation
times translational effciency
times a constant
equals quant HbSAg.

PLUS
transcription of surface antigen from integrated surface antigen containing HBV genome segments into hepatocyte chromosomes,

PLUS
a minute amunt of surface antigen ( less than 1%) stemming from is presence on Dane particles (circulating HBV virions)

Thus there is a basic good correlation between total liver cccDNA and the level of surface antigen.
If the surface antigen is UND there will be only very small remaining amounts of cccDNA.
Note that a tiny anount of cccDNA will almost always remain in the liver, ready to be reactivated under immune suppressive conditions like cancer chemotherapy or antirheumatic therapy, like TNFalpha blockers.

Note that a small amount of circulating surface antigen can be masked by a coexisting antibody, removing it from detection by immune complexing.

The transcriptional and translational activity is strongly influenced by the presence of cytokines, like INFalpha, more so by Interferon gamma.

High local IFNgamma concentrations close to a hepatocyte as produced by an epitope recognizing cd8 Tcell(CTL) will be able to activate intracellular machinery capable to eliminate HBV cccDNA minichromosomes form the cells in the direct vicinity of this event. This is likely the most critical event in the clearance of HBV from the liver, quantitatively much more important than the direct cytotoxic killing of infected cells.