来信：核苷（酸）类似物都不错，但没有足够的乙肝病毒清

StephenW

Letter: nucleos(t)ide analogues are good, but not sufficient for hepatitis B virus clearance – author's reply

    Y.-F. Liaw

Article first published online: 3 FEB 2016

DOI: 10.1111/apt.13510

© 2016 John Wiley & Sons Ltd

Issue
Alimentary Pharmacology & Therapeutics
Alimentary Pharmacology & Therapeutics

Volume 43, Issue 5, pages 655–656, March 2016


    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

Email: Y.-F. Liaw ([email protected])

Sirs,

The comments from Dr Afyon[1] on our article[2] are highly appreciated. The problems of indefinite or lifelong nucleos(t)ide analogues (Nuc) are more than those mentioned in the article and Dr Afyon's letter; problems not mentioned include lack of safety data beyond 5–10 years and negligible rate of hepatitis B surface antigen (HBsAg) seroclearance. More importantly, even in wealthy countries such as Singapore, lamivudine, which are known for its high resistant rate, is still used in 27% of the anti-viral therapies and only 25% of the patients on anti-viral medications were willing to pay the price of US $56 per week for a lifelong therapy.[3] Earlier research has also shown that cessation of anti-viral therapy with properly scheduled monitoring and retreatment is safe, and conceivably much safer than stopping therapy by patients themselves and defaulting on follow-ups. Such patients may encounter severe clinical relapse and even suffer from hepatic decompensation or mortality if retreatment is delayed.[4] The issue of stopping Nuc therapy has attracted more attention recently,[5] perhaps due to the realisation of these problems, and more studies are in process as presented in the most recent meetings of European and American liver associations.

We also agree that currently available Nucs have little effect on covalently closed circular DNA (cccDNA), and therefore are unable to eradicate hepatitis B virus (HBV) in the vast majority of the patients regardless of the potency or the duration of the drug usage. New drugs with action site(s) different from those of the Nucs are needed desperately for the ultimate goal of HBV eradication. As elaborated in Dr Afyon's letter, there are exciting advancement in the developments of such new drugs, and some agents in the pipeline have entered phase 2 or phase 3 clinical trials.[6]

StephenW

来信：核苷（酸）类似物都不错，但没有足够的乙肝病毒清除 - 作者的答复Y.-F.廖
文章首次在线发表时间：2016年2月3日
DOI：10.1111 / apt.13510
2016年©约翰·威利父子有限公司
问题
消化系统药理学和治疗
消化系统药理学和治疗
第43卷，第5期，655-656，2016年3月肝癌研究单位，长庚医院，医学长庚大学，台湾台北页
电子邮件：Y.-F.廖（[email protected]）
先生们，
从阿菲永博士[1]在我们的文章[2]意见高度赞赏。无限期或终身核苷的（NUC）的问题（）类似物比文章和兰宁医生的信中提到的那些多;没有提到的问题包括超过10年缺乏安全性数据和B型肝炎表面抗原（HBsAg）血清学清除的可忽略的速率。更重要的是，即使在富裕的国家，如新加坡，拉米夫定，这是它的高耐药率已知的，仍然是在抗病毒治疗的27％使用，只有25％的患者在抗病毒的药物，愿意支付美国56 $每周为终身治疗的价格。[3]早期的研究还表明，抗病毒治疗的停止，在正确计划的监测和再治疗是安全的，可以想象比病人停止治疗自己和拖欠后续更安全-UPS。这样的患者可能会遇到严重的临床复发，甚至肝功能失代偿或死亡率受苦，如果再处理被延迟。[4]停止国统会治疗的问题已经引起了更多的关注最近，[5]也许是由于实现的这些问题，更多的研究在过程在最近欧洲和美国肝脏协会的会议上提出。
我们还同意，目前Nucs对共价闭合环状DNA（cccDNA的）影响不大，因此无法在绝大多数患者根除乙肝病毒（HBV），无论效力或药物使用的持续时间。用行动网站（）不同于Nucs不同的新的药物都迫切需要消除HBV的终极目标。正如在阿菲永博士的信中阐述，也有这样的新的药物的发展令人兴奋的进步，在管道部分代理商已进入第二阶段或第三阶段​​临床试验。[6]