对REP9AC、DV601等治愈乙肝科学研究的看法

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三国杀

没看懂呀，这是阻断乙肝哪个方面，原文出处在哪里？

三国杀

而且8个人，例数太少了吧

StephenW

studyforhope 在Medhelp上 回答 Rep 9AC问题:

[4est]:
Let assume that we have HbeAg negative, HbsAg suppress by Rep9Ac and DNA supress by antivirals. so, this is the best case for a chronic carrier (no e or s antigen for divert immune answer, no DNA means no new viruses), but also in this situation the cccDNA will remain in the liver cells. how this will be manage?
Can we assume that because we don't have s and e antigens the immune system will target the infected liver cells and destroy them ?

[studyforhope]:
That is the basic concept. In addition to the direct targeting by cd8 cytotoxic Tcells, the local phagocytosis of virions and debris from necrotic liver cells containing HBV proteins will allow presentation of the classII  peptide epitopes on the surface of Macrophages and Kupffer cells  to cd4 helperTcells in the liver, with a strong local cytokine response that will help in the noncytolytic clearance  of hepatocytes fromm HBVcccDNA.

One problem is likely that the longstanding exhaustion of the  s antigen specific T-cell clone repertoire (many many years of periphery flooding with e and s antigens) will require a substantial time frame of regeneration of this immune response, particularly in older patients and those with a longer chronic infection. Thus a longer supression of s-antigen release by REp 9AC might be necessary  to allow targeted immune recovery in these patients.
Aside from protection against adaptive immune evasive epitope mutations by antivirals, it might also be advisable to accelerate the regeneration of the blunted adaptive immune response - TandB cells-  by therapeutic vaccinations once the s-antigen is negative.

Regarding new developments on the horizon, there is a therapeutic HBV vaccine by Dynavax, that could be used eg in the context above. Replicor and Myrcludex remain the most promising partial attack modes against HBV at this moment.
The liver concentrating tenofovir would be a great element of progress, since reduction in antiviral toxicity is a major concern, consdering the need for long term use.
Nitazoxanide thus far - see Stefs progress reports- seems to be of weak effectiveness, at least at the dosing that is low enough for comfort.

Substances like squalamine might be virus propagation blocking to a certain degree, but the effect on the reduction of the cccDNA hepatocyte population is unlikely to be better than the one with antivirals. It is too early to make any specific predictions.

StephenW

[4est]:
Rep9AC will suppress HBsAg and in this case we can produce HBsAb ? and what happen if ccDNA will remain in some liver cells ? will be enough HBsAb to suppress HBsAg after the Rep9Ac treatment is stooped ? .

[studyforhope]
Providing that enough s antigen specific B cells are left or have recovered, there will be an antiHbs antibody titer.
If, after REP9AC is stopped only a tiny amount of infected cccDNA containing cells are left after immune clearance, then the antibody will be sufficient to neutralize this very very small amount of surface antigen.
The key is the suffcient reduction of the cccDNA containing hepatocye pool PLUS a remaining population of HBV antigen specific Tcells in the liver to help supress the synthetic and replicative activity of this small cell pool by a local permanent cytokine milieu, that will inhibit transcription , replication and possibly translation of the HBVgenomes that will still reside in the liver, just as is the case with persons with acute recovered Hepatitis B - for a lifetime, without outside intervention.

It needs to be understood, that the antiHbS antibody is only protecting against reinfection. The key long term controlling factor is a long lasting antigen specific Tcell response residing in the liver.

Only in case of a cancer chemotherapy or intense antinflammatory therapy with TNFalpha inhibitors such remnant HBV clusters tend to regrow and reactivate, since the permanent watchdog forces are now of diminshed activty - a process called REACTIVATION. It is now becoming routine to protect against such reactivations in prior acute recovered HBV cases or chronic cleared HBSseroconverters with temporary antivirals during such treatments.                           

cwy121

回复 StephenW 的帖子

我靠，你是中国人还是外国人啊？不要老整英文嘛 ，看不懂啊！

走遍四方

回复 cwy121 的帖子

朋友别怪他，没办法，最先进的都是英文的。。。木有法子。。

alex1234

变异率太高了。。。。

kaorusai

刚在网上看到了关于Myrcludex的这样一个信息
The completion of Phase 1 and the start of the „proof-of-concept“ Phase 2 study are planned for 2012.

http://www.en.high-tech-gruenderfonds.de/2011/05/high-tech-grunderfonds-invests-in-a-novel-hepatits-b-compound/

这样下去Myrcludex要是能成功的话应该比REP9AC要快！

StephenW

kaorusai 发表于 2011-10-3 13:17
刚在网上看到了关于Myrcludex的这样一个信息
The completion of Phase 1 and the start of the „proof-of- ...

"这样下去Myrcludex要是能成功的话应该比REP9AC要快！" - 这是可能。但我们应该记住，Mycrludex本身是不够治愈.

Myrcludex presentation at the San Francisco liver conference.
Conclusions: Myrcludex-B showed strong capacities to prevent HBV spreading in vivo. Since maintenance of chronic HBV infection involves a dynamic turnover between cells that are cleared by the immune system and cells that become newly infected, the use of drugs preventing hepatocyte re-infection, possibly in combination with other HBV-drugs, may represent a new effective antiviral concept also in the setting of chronic infection.

Myrcludex旧金山肝会议的演示。
结论：Myrcludex- B的表现出较强的防止乙肝病毒在体内扩散的能力。
由于慢性乙肝病毒感染的维护包括一个动态的营业额是由免疫系统，并成为新感染的细胞，防止肝细胞再感染的药物的使用可能在与其他乙肝病毒药物的组合，清除细胞之间，可能代表了一种新的有效抗病毒药物的概念在慢性感染的设置。