NATAP/EASL: 恩替卡韦HBV cccDNA

StephenW

Subject: NATAP/EASL: Entecavir & HBV cccDNA
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> Impact of Entecavir Versus Lamivudine on Hepatic HBV Covalently Closed-Circular DNA and Total Hepatic HBV DNA in Nucleoside-Naïve HBeAg Positive Chronic Hepatitis B Patients
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> Reported by Jules Levin
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> EASL 2013 Amsterdam April 24-28
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> Scott Bowden1, Stephen Locarnini1, Ting-Tsung Chang2, You-Chen Chao3, Kwang-hyub Han4, Robert G. Gish5, Robert de Man6, Cyril Llamoso7, Hong Tang8
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> 1Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; 2National Cheng Kung University Medical College, Tainan, Taiwan; 3Tri-Service General Hospital, Taipei, Taiwan; 4Severance Hospital, Seoul, Republic of Korea; 5University of California San Diego Health System, San Diego, CA, USA; 6Erasmus Medical Center, Rotterdam, the Netherlands; 7Bristol-Myers Squibb, Research & Development, Wallingford, CT, USA; 8Bristol-Myers Squibb, Research & Development, Princeton, NJ, USA
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> Chronic HBV infection is associated with a pool of stable, covalently closed-circular HBV DNA (cccDNA) inside the nuclei of infected
> hepatocytes2
> • Hepatic cccDNA can lead to HBV reactivation after HBsAg clearance2
> • Hepatic cccDNA and chromosomal HBV integration (together with immune-mediated liver inflammation) are believed to contribute to
> HCC development3−5
> • Reduction or elimination of cccDNA with anti-HBV therapy may provide clinical benefits such as:
> – Lower risk of HBV reactivation after seroclearance6
> – Lower risk of HCC development6,7
> – Lower risk of HBV recurrence and improved survival after liver resection or transplantation8,9
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> Here, we describe the results of an analysis comparing the effects of ETV (entecavir) and LVD (lamivudine) on hepatic cccDNA and total hepatic HBV DNA levels in nucleos(t)ide-naïve HBeAg(+) patients
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> Summary and Discussion
> • Virologic and histological response rates were greater with ETV than with LVD over 48 weeks
> • ETV resulted in greater reductions of hepatic HBV cccDNA and total hepatic DNA levels from baseline to Week 48 than LVD
> – Blocking the intracellular conversion of relaxed circular genomic DNA to cccDNA using a potent antiviral agent such as ETV exerts a significantly greater effect on the pool of cccDNA molecules than an agent with a lower potency
> • Baseline HBV cccDNA was associated with baseline serum and total hepatic HBV DNA, and HBV genotype F
> • Reduction in hepatic HBV cccDNA was associated with baseline serum HBV DNA and ALT, on-treatment clearance of serum HBV DNA, total hepatic HBV DNA, ALT, and HBeAg, and improvement in liver inflammation
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> Conclusions
> • At Week 48, treatment with ETV was superior to LVD in reducing hepatic HBV cccDNA and total hepatic HBV DNA from baseline
> • Lower baseline HBV cccDNA was associated with lower baseline serum HBV DNA, lower baseline total hepatic HBV DNA, and HBV genotype F
> • Greater HBV cccDNA reduction at Week 48 was associated with lower baseline serum HBV DNA, higher baseline ALT, greater on-treatment decreases in serum HBV DNA, total hepatic HBV DNA, Knodell necroinflammatory score and ALT, and HBeAg loss

StephenW

慢性HBV感染与感染的细胞核内稳定，共价闭合圆形HBV DNA（cccDNA的）一池
> hepatocytes2
>•肝cccDNA的可导致HBV再激活乙肝表面抗原clearance2后
>•肝的cccDNA的染色体整合型HBV（连同免疫介导的肝脏炎症）被认为有助于
>肝癌开发3-5
>•减少或消除cccDNA的抗乙肝病毒治疗提供临床益处，如：
>  - 低风险HBV再激活seroclearance6后
>  - 下，肝癌发展的危险
>  - 低风险肝切除后或transplantation8 9乙肝复发，提高生存率
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在这里，我们描述的结果的分析比较肝cccDNA的（恩替卡韦ETV）和LVD（拉米夫定）和全肝HBV DNA水平在核苷（T）IDE天真的HBeAg（+）患者的影响
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>总结和讨论
病毒学和组织学应答率分别为48周以上恩替卡韦比LVD
>•ETV导致更大的削减比LVD肝HBV cccDNA和全肝DNA水平从基线到48周
>  - 阻断细胞内转换宽松的圆形基因组DNA cccDNA的效力较低，使用强效抗病毒药物如ETV代理人以外施加显着影响更大对cccDNA的分子池
•基线HBV cccDNA的是与总基线血清肝HBV DNA和HBV F基因型
>•减少肝HBV cccDNA的是与基线血清HBV DNA和ALT，血清HBV DNA，总肝HBV DNA，ALT和HBeAg治疗间隙，改善肝脏炎症
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>结论
>•恩替卡韦治疗48周时，减少肝HBV cccDNA和总肝HBV DNA从基线明显优于LVD
>•基线HBV cccDNA的是与较低的基线血清HBV DNA，较低的基线总肝HBV DNA和HBV F基因型
>•大HBV cccDNA的48周减少是与较低的基线血清HBV DNA的基线ALT更高，更大的治疗降低血清HBV

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