贾继东教授 - “在中国的临床应用Telbiduvine”

StephenW

http://onlinelibrary.wiley.com/doi/10.1111/jvh.2013.20.issue-s1/issuetoc?dmmsmid=72748&dmmspid=22486861&dmmsuid=1932682
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Journal of Viral Hepatitis

JOURNAL OF VIRAL HEPATITIS

Click here to read our Chinese Supplement on the treatment of Hepatitis B ‘Clinical Application of Telbiduvine in China’ edited by Professor Jidong Jia. This focusses on the treatment of Hepatitis B in a resource-poor country and contrasts are also drawn with what is happening elsewhere in the world via an editorial by the editor of JVH, Professor Howard Thomas.

中国病毒性肝炎
作者：病毒性肝炎

点击这里阅读我们的中国副刊上治疗乙型肝炎的临床应用在中国的教授冀东佳编辑Telbiduvine。这论点集中在一个资源贫乏的国家和对比治疗乙型肝炎发生的事情在世界其他地方通过一篇社论主编，教授霍华德·托马斯JVH绘制。

StephenW

Chronic hepatitis B (CHB) poses a serious public health burden in Asian-Pacific countries including China [1]. To promote communication between hepatologists in China and outside of the world, epidemiology, prevention, diagnosis and management of CHB in China were published in a special supplement of JVH in 2010 [2].

Today, treatment for CHB is still an enormous challenge in China, although the prevalence of HBsAg in general population has declined from 9.75% to 7.18% due to successful universal HBV vaccination in newborns [1]. Because most patients who receive NA may require long-term therapy to prevent the progression of liver disease, both American and European guidelines recommend entecavir and tenofovir as first-line oral agents due to their potent antiviral effect and low risk of drug resistance [3, 4]. An expert review paper also highlights the importance of starting treatment with high barrier to resistance: minimizing the development of resistance, preserving future treatment options and maximizing the chances of long-term treatment success [5]. However, in Asia-Pacific consensus statement, all nucleos(t)ide analogs are listed as first-line therapy, although high-potent and low-resistance agents are preferred [6]. In the 2010 update of China guideline on the management of CHB, a similar recommendation is adopted [1]. This compromise is mainly due to the highly heterogeneous economic situations across this region of the world or even across different parts of a single country, where potent antiviral agents such as entecavir or tenofovir may not be available, not reimbursable or not affordable [7].

In China, ‘Road-map’ concept is an acceptable approach that is to start with a less-expensive antiviral drug (such as lamivudine, adefovir or telbivudine) and add-on or switch-to another drug for those with a suboptimal HBV DNA response [8]. Indeed, an interim analysis of a prospective, randomized, controlled clinical study performed in China shows that the efficacy of telbivudine is strengthened and resistance is reduced by adding adefovir [9].

With the same aim of the 2010 supplement, this supplement of JVH reports clinical and experimental studies of CHB, with a focus on the clinical application of telbivudine in China where this agent is still widely prescribed.  I hope these review and original articles will shed light on or at least give a different look at the management of CHB in resource-constrained countries.

慢性乙型肝炎（CHB）对包括中国在内的亚太国家的一个严重的公共卫生负担[1]。为了促进肝病在中国和世界之外，流行病学，预防，诊断和管理慢性乙肝在中国的之间的沟通结果发表在2010年的一个特殊的补充JVH [2]。

今天，慢性乙型肝炎的治疗是在中国仍然是一个巨大的挑战，虽然在一般人群的HBsAg的患病率已经从9.75％下降至7.18％，由于成功普及新生儿乙肝疫苗接种[1]。由于大多数患者接受NA可能需要长期的治疗，以防止肝病进展，美国和欧洲的指引建议作为一线口服制剂，由于其强大的抗病毒效果和低风险的耐药性分析[3，恩替卡韦和替诺福韦4]。专家审评文件还强调高耐药屏障开始治疗的重要性：减少发展的阻力，保持未来的治疗选择和长期治疗成功[5]的机会最大化。然而，在亚太地区的共识声明，所有核苷（酸）类似物列为第一线治疗是首选，虽然高有力和低电阻剂[6]。慢性乙型肝炎的管理准则，中国在2010年更新，采用了类似的建议[1]。主要是由于这个妥协是高度异质性的世界在这一地区的经济形势，甚至可以跨越不同部位的一个单一的国家，强效抗病毒药物如恩替卡韦或替诺福韦，不予报销或负担不起[7]。

在中国，'路线图'的概念是一个可以接受的方法是启动一个不太昂贵的抗病毒药物（如拉米夫定，阿德福韦或替比夫定），并添加或切换到另一种药物与一个次优的HBV DNA响应[8]。事实上，在中国进行了一项前瞻性，随机，对照临床研究的中期分析显示，替比夫定的疗效得到加强和阻力减少增加阿德福韦[9]。

随着2010年的补充相同的目的，这个JVH补充报告慢性乙型肝炎的临床和实验研究，替比夫定的临床应用，在中国，这种代理仍然广泛的处方上的焦点。我希望这些审查和原创文章揭示，或至少在慢性乙型肝炎的管理在资源有限的国家给予不同的外观。

StephenW

In this issue of JVH, we have published a series of articles describing some current practises in China where the majority of patients with CHB live. Professor Jia and most Chinese physicians acknowledge the fact that the use of the most potent drugs, tenofovir and entecavir, will minimize the risks of development of viral resistance, but these are expensive and not currently widely available in China. As a result, treatment has often been started with lamivudine or telbivudine which are less expensive. This has resulted in many patients developing viral resistance and recurrence of progressive liver disease within the first 5 years of treatment, in a disease where viral suppression is needed for many decades. Thus, although some patients with cirrhosis may derive clinical benefit initially, over the long term, the disease will progress with a return of significant risk of death from hepatic decompensation and HCC.

To address these problems, a recent WHO Expert group (Wiersma et al. [1]) have emphasized the need for governments of countries with a high prevalence of HBV infection, to urgently address the issue of CHB with the same vigour as is currently given to HIV infection. Indeed the medical infra-structure developed for management of HIV will facilitate delivery of care to those with HBV.

In the meantime, there is logic in moving away from the economically driven ‘Road Map’ approach where adefovir is added to lamivudine or telbivudine when suppression of HBV DNA is inadequate or when recurrence has occurred, to one where patients start on combination therapy. Against a background of a need for viral suppression of many decades, the early addition of adefovir adds very little to overall cost. Interestingly, there has also been a resurgence of interest in pegylated interferon therapy, a drug which is immune-stimulant as well as having viral suppressive actions free from the risk of development of resistance. Furthermore, because interferon therapy is limited to one year duration and results in around one-third of HBe antigen positive patients achieving a sustained response without need for further viral suppressive therapy, it is cost-effective. The ultimate drug choice will be dependent on recognition of the long-term needs of these patients and the negotiation of affordable pricing of the most potent drugs or combinations of less potent drugs. JVH will continue to publish studies reporting what is happening in this area with the hope and expectation that the benefits of these effective anti-viral drugs will be brought to bear on this potentially lethal infection in the developing world. To this end, we will shortly be publishing in a supplement, a review of the Hepatitis B and C Policy Group meeting looking at these conditions in the Balkans and Mediterranean countries including North Africa, where similar issues arise.

在这个问题JVH，我们已经发表了一系列文章，描述目前的一些做法，在中国，大多数CHB患者生活。佳教授和大多数中国医生承认一个事实，即使用最有效的药物，替诺福韦和恩替卡韦，将最大限度地减少病毒耐药性的发展风险，但这些都是昂贵的，而不是目前广泛使用在中国。其结果是，治疗经常与拉米夫定或替比夫定一些较廉价的开始。这导致了发展的第一个5年的治疗病毒性和内渐进肝病复发，需要几十年来抑制病毒的一种疾病，其中许多患者。因此，尽管有些肝硬化患者可能最初获得临床获益，从长期来看，本病会进步明显肝功能失代偿和肝癌的死亡风险与回报。

为了解决这些问题，最近世卫组织专家小组的（维尔斯马等[1]）强调，有必要对HBV感染高流行国家的政府，迫切解决的问题具有相同的活力目前CHB感染艾滋病毒。事实上，医疗基础设施开发管理艾滋病毒HBV方便的照顾和关怀。

与此同时，在远离经济驱动的“路线图”的方法，加入阿德福韦抑制HBV DNA不足或发生复发时，患者开始联合治疗对拉米夫定或替比夫定是有一个逻辑。针对需要几十年的病毒抑制的背景下，早期加用阿德福韦增加很少的整体成本。有趣的是，同时也出现了死灰复燃的兴趣聚乙二醇干扰素治疗，药物是免疫兴奋剂，以及具有对病毒的抑制行动，从发展的阻力的风险。此外，由于干扰素治疗一年实现持续应答，而不需要作进一步的病毒抑制疗法抗HBe抗原阳性患者约三分之一的持续时间和结果是有限的，它是符合成本效益的。最终确认这些患者的长期需求和负担得起的价格的谈判的最有力的药物或药物组合不太强的药物，药物的选择将取决于。 JVH将继续发布研究报告正在发生的事情在这方面的希望和期待，这些有效的抗病毒类药物的好处将被带到这个潜在的致死性感染在发展中国家承担。为此，我们将在短期内发布的补充，乙型和丙型肝炎的政策小组会议在巴尔干和地中海沿岸国家包括北非发生类似的问题，其中在这些条件的评论。

StephenW

Clinical Application of Telbivudine in China. Guest Editor: Prof. Jidong Jia. This supplement was kindly sponsored by Novartis

    EDITORIALS
    You have free access to this content
    A different look at the management of chronic hepatitis B in a resource-constrained country (page 1)

    J. Jia

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12056
      
    Treatment of chronic Hepatitis B in resource-constrained countries: an economic solution is required (page 2)

    Howard Thomas

   
    REVIEW ARTICLES
   
    Telbivudine treatment in chronic hepatitis B: experience from China (pages 3–8)

    H. You and J. Jia

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12058
        
    Telbivudine treatment is associated with high hepatitis B e antigen seroconversion and immune modulatory effects in chronic hepatitis B patients (pages 9–17)

    G.-Q. Wang, Y.-P. Ding and Y.-H. Dong

   
    Rapid downregulation of programmed death-1 and interferon-γ-inducible protein-10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B (pages 18–26)

    F.-Q. Hou, X.-J. Wu, Y. Wang, J. Chen, Y.-Z. Liu, Y.-Y. Ren, G. Song, Y.-P. Ding, M. Yu and G.-Q. Wang

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12060
        
    PD-1/PDL1 and CD28/CD80 pathways modulate natural killer T cell function to inhibit hepatitis B virus replication (pages 27–39)

    X. F. Wang, Y. Lei, M. Chen, C. B. Chen, H. Ren and T. D. Shi

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12061
      
    Efficacy and safety of telbivudine plus adefovir dipivoxil combination therapy and entecavir monotherapy for HBeAg-positive chronic hepatitis B patients with resistance to adefovir dipivoxil (pages 40–45)

    Jia-Jie Lu, Kai Liu, Yuan-Ji Ma, Juan Wang, En-Qiang Chen and Hong Tang

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12062
      
    Efficacy of telbivudine treatment for hepatitis B e antigen-positive chronic hepatitis B patients with poor response to adefovir dipivoxil (pages 46–51)

    Y. Li, Y. Zhang, J.-P. Wang, J.-Q. Lian and X.-F. Bai

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12063
        
    Efficacy of sequential use of telbivudine in hepatitis B e antigen-positive chronic hepatitis B patients with partial responses to pegylated interferon: a pilot study (pages 52–57)

    Z. Huang, Z. Zhao, Y. Zheng, L. Peng, C. Lin, H. Deng and Z. Gao

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12064
        
   
    Forty-eight-week retrospective study of telbivudine and lamivudine treatment in patients with hepatitis B-related cirrhosis (pages 58–64)

    Z. Han, Y. Shi, J. Zhu, Y. Chen, F. Yin, L. Xia, G. Luo, Z. Gao, J. Liu, G. Jia, C. Li, X. Zhou and Y. Han

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12065
      
    Safety of telbivudine treatment for chronic hepatitis B for the entire pregnancy (pages 65–70)

    M. Liu, H. Cai and W. Yi

    Article first published online: 4 MAR 2013 | DOI: 10.1111/jvh.12066
        

替比夫定在中国的临床应用。客座编辑：冀东佳教授。由诺华公司慷慨赞助本补充

   
不同的外观在慢性乙型肝炎的管理在资源有限的国家（第1页）

    J.佳

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12056
        
治疗慢性乙型肝炎在资源有限的国家：一个经济的解决方案是必需的（第2页）

    霍华德·托马斯

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12057
        
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   替比夫定治疗慢性乙型肝炎：来自中
替比夫国的经验（第3-8页）

    H.您和J.佳

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12058
        
替比夫定治疗与高B型肝炎e抗原血清学转换和免疫调节作用，在慢性乙型肝炎患者（第9-17页）

    G.-Q.王Y.-P.丁和Y.-H.的董

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12059
        

快速程序性死亡-1和γ-干扰素诱导蛋白10表达的下调与有利的结果，在抗病毒治疗慢性乙型肝炎（第18-26页）

    F.-Q.侯X.-J.吴，王华，陈军，Y.-Z.刘Y.-Y.仁，G.宋，Y.-P.丁，M.羽和G.-Q.的王

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12060
      

PD-1/PDL1和CD28/CD80通路的调节自然杀伤T细胞的功能，抑制乙肝病毒复制（第27-39页）

    XF王，华磊，陈米，陈CB，H.仁和TD轼

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12061
      
替比夫定联合阿德福韦酯联合治疗和恩替卡韦单药治疗HBeAg阳性慢性乙型肝炎患者耐阿德福韦酯（第40-45页）的疗效和安全性

    吕佳杰，刘凯，马源吉，王娟，陈强恩和唐虹

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12062
        
替比夫定治疗的疗效乙肝e抗原阳性的慢性乙肝患者与阿德福韦酯反应不佳（第46-51页）

    Y. Y.李，张，J.-P.王J.-Q.廉和X.-F.的白

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12063
        
乙肝连续使用替比夫定疗效É抗原阳性的慢性乙肝患者与聚乙二醇干扰素部分响应：一项试验性研究（第52-57页）

    Z.黄，Z.赵，郑华，L.鹏，三林，邓H.和Z高

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12064
        
四十八个星期的回顾性研究中，替比夫定和拉米夫定治疗的患者与乙肝相关肝硬化（第58-64页）

    Z.汉族，G. L.夏，华石，朱军，陈华，楼贤，罗高，Z.，J.刘贾，G.，C.李周，X.和Y汉

    首次在网上公布：2013年3月4日| DOI：10.1111/jvh.12065
        
安替比夫定治疗慢性乙型肝炎的整个孕期（第65-70页）

    M.刘，蔡H. W.易

    文章首次在线发表时间：2013年3月4日| DOI：10.1111/jvh.12066
        

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