[Corrections by Studyforhope] How REP 9AC works.

StephenW

灰天 发表于 2011-8-15 21:29
hbsag>250,hbsab8.9,e抗原0.46，e抗体0.04.核心抗体9.9，IGM0.1,肝功基本正常，b超正常，dna正常.....什么 ...

我不是专家，我给你我个人的意见。
通常情况下，乙肝表面抗体需将超过10才有意义的。
我建议在几个月后你再次测试您的乙肝表面抗原和乙肝表面抗体。
重要的是肝功正常, dna ~ 0.

灰天

谢谢

StephenW

Some more explanations from studyforhope. [UND - I think it means undetectable]

1. REP 9AC is best used with an antiviral (that reduces viral load and thus re-infection)?

A difficult question, because a reduction in viral load by the antiviral is also often followed by lower immune activity, that might delay the reawakening of the immune response to the surface antigen after it has been blocked by REp9AC from flooding the system.
Nevertheless, the capacity of HBV to grow back against the reawakened surface epitope Tcell mediated clearance effect should be much weaker with an antiviral in place. HBV is a dynamic disease and the dramatic reduction by antivirals of the replicative capacity of  HBV should help the clearance dynamics.

The blockage of reinfection by antivirals might not be as effective as one might think. The virus overproduces virions tens of thousandfold over the amount needed to fully reinfect. Not only is the UND status misleading insofar as the detection methods still have limited sensitivity and UND could still mean a production of eg 50000 dane particles a day, but yet another critical effect has to be considered. Freshly produced virions in particular will readily infect a neighboring hepatocyte cell from the space of Disse, but also circulating virions will be rapidly absorbed and removed by the liver by its affinity to the preS1myr  binding receptor at the hepatocyte surface. To put it simple, the liver will act like a gigantic affinity absorbing column/mass, removing/ clearing Dane particles from the circulation until it is saturated. Thus even real UND with more sensitive methods might not mean that there is still a large amount of reinfection/remnant virion production  going on.


2. REP 9AC is best used with an entry inhibitor like Myrcludex?
This could be an ideal combination, because any freshly produced or cleared cell will be protected from reinfection, allowing slow but consistent reduction of viral infestation of the liver.
Here is however another critical argument regarding the replacement of immune cleared cells by fresh uninfected hepatocytes; While the mainstream thinking is that hepatocytes are replaced by division from so called satellite cells embedded in the liver ( 'liver stem cells") others think that regular hepatocytes will divide once the regnerative impulse/signal  from Hepatocyte Growth Factor is sensed to replace a shrinking liver mass. The dividing "mother" cell is likely infected, and since there are typically 10 to 30 HBV cccDNA molecules in the nucleus, these will be distributed into the daughter cells, which then, bingo, are already infected from their "birth".
Antivirals typically reduce the amount of cccDNA, but nor dramatically, at best about 10 times.This might still help in this scenario.



3. REP 9AC, by reducing the number of HBsAg particles, is sufficient to allow the immune system to do its job in clearing hbv?

This will depend on the vigor and breath of the anti surface Tcell  (cd8 - cytotoxic/killer as well as cd4 helper Tcells) and later B cell response. It has been tolerized by oversupply with antigen for a long time, most clones will be exhausted or lost. Thus a less than perfect SVR rate can be explained by an insuffcient recovery of that system. It will take time to regenerate, reawake, possibly by the novo supply from the thymus. Some think that the surface antigen mainly acted as a suppressor of innate immunity, that this innate immunity will restart once the mitigating protein hasd disappeared from the circulation. Chisari and the majority of HBV immunology specialist place more emphasis on the adaptive, specific response, since it allows targeted removal of HBV protein producing infected cells. In reality, innate immunity is the danger sensing promotor of adaptive imunity, the two work in intimate collaboration and therefore both need to be quite functional for a successful clearance event.

4. What is the method used to deliver REP 9AC into the liver cells?
From what was  heard at the European meeting, it is by weekly infusion.