CCC-DNA和总肝HBV DNA核苷初治的HBeAg阳性慢性乙型肝炎患者的肝

StephenW

hepatic ccc-DNA and total hepatic HBV DNA in nucleoside-naïve HBeAg positive chronic hepatitis B patients       
                        A poster study presented during the EASL meeting showed that treatment with entecavir was superior to lamuvidine in reducing hepatic cccDNA (covalently closed-circular DNA) and total hepatic viral load in patients with HBV-infection.
       
                        In hepatitis B, one of the treatment challenges is the persistence of one of the key replicative markers of the hepatitis B virus in the liver, called the covalently closed-circular HBV DNA (cccDNA) of the virus, which is the transcriptional template and the driving force of the virus. Hepatic cccDNA and chromosomal HBV integration, together with liver inflammation resulting from the immunological reaction to the infection, are believed to contribute to HCC development.
       
                        Reducing cccDNA levels might help eradicate hepatitis B
       
                        Reducing or eliminating cccDNA with anti-HBV therapy may provide clinical benefits such as lowering the risk of HBV reactivation after seroclearance, lowering the risk of HCC development, but also lowering the risk of HBV recurrence and improving survival after liver resection or transplantation.
       
                        “Most treatments usually have little or no effect on cccDNA levels, however we believe that if we can reduce the cccDNA levels then we’ll actually move closer towards curing or eradicating Hepatitis B,” said Stephen Locarnini, from North Melbourne in Australia.
       
                        Entecavir superior to lamivudine at reducing cccDNA levels
       
                        Locarnini’s team compared the effects of lamivudine (a low potency/low genetic barrier drug) and entecavir (a more potent/high genetic barrier drug) on hepatic cccDNA and total hepatic HBV DNA levels. The researchers collected biopsies from the livers of 305 patients with evaluable hepatic HBV cccDNA and total hepatic HBV DNA pairs at baseline, and after 48 weeks of treatment with either drug.
       
                        Linear regression adjusted for baseline levels revealed mean log10 changes in hepatic cccDNA and total hepatic HBV DNA: The findings showed that, compared with LVD, ETV led to significantly greater reductions of hepatic cccDNA (-0.2 (-0.3, -0.1, 95% CI, p<0.0033) and total hepatic DNA levels (-0.5 (-0.6, -0.3, 95% CI, p<0.0001) at Week 48 from baseline (Slide 15).
       
                        “Blocking the intracellular conversion of relaxed circular genomic DNA to cccDNA using a potent antiviral agent such as entecavir exerts a significantly greater effect on the pool of cccDNA molecules than an agent with a lower potency,” explained Locarnini.
       
                        Written by Clementine Wallace, based on poster abstract 759, presented by Stephen Locarnini, from North Melbourne, Australia, also interviewed during the EASL congress 2013 in Amsterdam.
                        May 3rd, 2013
       

StephenW

CCC-DNA和总肝HBV DNA核苷初治的HBeAg阳性慢性乙型肝炎患者的肝



海报EASL会议期间提出的研究表明，恩替卡韦治疗是优于，lamuvidine减少肝的cccDNA的（共价闭合环状DNA）和全肝病毒载量HBV感染患者。



在B型肝炎，治疗的挑战之一是在肝脏中的B型肝炎病毒复制的关键标志物的持久性，称为共价闭合圆形的HBV-DNA（cccDNA的）的病毒，这是转录的模板和驱动力的病毒。肝共价闭合环状DNA和染色体整合型HBV，连同肝组织炎症导致的感染的免疫学反应，被认为是向肝癌的发展。



减少cccDNA水平可能有助于消除B型肝炎



cccDNA的抗乙肝病毒治疗减少或消除可能提供的临床益处，如降低HBV再激活的风险转阴后，降低肝癌发展的风险，但也降低了乙肝病毒复发的风险，并改善肝切除或移植后的生存。



“大多数治疗通常有很少或没有影响，但我们相信，如果我们能够减少cccDNA水平，那么我们将实际移动接近固化或消除乙型肝炎cccDNA水平，”斯蒂芬说，从澳大利亚北墨尔本Locarnini。



恩替卡韦优于拉米夫定降低cccDNA水平



Locarnini的团队比较肝cccDNA的效力低/低基因屏障的药物（拉米夫定）和恩替卡韦（一种更有效的/高基因屏障的药物）和全肝HBV DNA水平的影响。研究人员收集了从评估肝HBV cccDNA和全肝HBV DNA双基线的305例肝脏活检，经过48周的治疗，这两种药物。



线性回归基线水平调整透露cccDNA的肝和全肝HBV DNA平均log10的变化：研究结果表明，与LVD相比，ETV导致肝cccDNA的显着更大的削减（-0.2（-0.3，-0.1，95％CI ，P <0.0033）和总的肝DNA水平（-0.5（-0.6，-0.3，95％CI，P <0.0001），第48周从基线（幻灯片15）。



“阻断细胞内转换宽松的圆形基因组DNA cccDNA的使用强效抗病毒药物如恩替卡韦剂效力较低的cccDNA的分子比池施加显着的影响更大，，解释Locarnini。”



写的克莱门汀华莱士，基于759，海报抽象提出斯蒂芬Locarnini，从北墨尔本，澳大利亚，2013 EASL代表大会期间还采访了在阿姆斯特丹。

2013年5月3日

咬牙硬挺

抗病毒能降低cccdna？真假啊

StephenW

回复 咬牙硬挺 的帖子

间接的影响。这是我个人的解释:

A 增加cccDNA池的因素:
1.在受感染的细胞的细胞质中产生新的病毒衣壳（HBVDNA里面）
2.从肝细胞以外的新的病毒颗粒- 它们是来自相邻受感染的肝细胞

B 降低cccDNA池的因素:
1. 肝细胞周转(turnover)期间细胞的分裂(cell division)

抗病毒药物，尤其是强效的抗病毒药物, 可减少或阻止 A.
当B> A, cccDNA的池下降.

咬牙硬挺

回复 StephenW 的帖子

你说的在逻辑上有道理，推理家啊^_^)Y