临床医生用于治疗HCV多1线;挑战是实现

StephenW

www.natap.org
Clinicians Have Multiple First-line Options for Treating HCV; Challenge is ImplementationPosted By: AASLD on: November 15, 2015

http://www.livermeetingtoday.org/clinicians-have-multiple-first-line-options-for-treating-hcv-challenge-is-implementation/


A succession of discoveries has led to infection cure rates of better than 90% in the quarter century since the discovery of the hepatitis C virus (HCV).
[img=202,260]https://ci3.googleusercontent.com/proxy/__7kWNKbLDalzlcbinhY2pQwfIgGmIynNzYNFpQZ4_eWHjX1CtJFC0oRnINO7KI_04NI5suw7hQoY9BSJyhKQo6yUhMEGL5WZMz9Woiy1TWH18WpcJhn5H4cdm1Sw7PD2g=s0-d-e1-ft#http://www.livermeetingtoday.org ... /11/pawlotskyPG.jpg[/img]Jean-Michel Pawlotsky, MD, PhD

At Session I of the AASLD Postgraduate Course on Saturday, Jean-Michel Pawlotsky, MD, PhD, of the Henri Mondor University Hospital, University of Paris-Est, in France, reviewed the four direct-acting anti-viral (DAA) drugs now available and how those drugs are used in a trio of interferon (IFN)-free combinations to treat and cure HCV. International guidelines no longer recommend treatments containing IFN as first-line therapy.
“Notwithstanding the respective costs of these options, IFN-free regimens are the best options when available because of their virological efficacy, ease of use and tolerability,” Dr. Pawlotsky said.
NS3-4A protease inhibitors (first-wave telaprevir, boceprevir; second-wave simeprevir, paritaprevir/r, asunaprevir and vaniprevir) shut the virus life cycle. NS5A inhibitors (daclatasvir, ledipasvir, ombitasvir ; second-wave elbasvir, velpatasvir) disorganize the replication complex and also block the assembly and release of viral particles.
Non-nucleoside inhibitors (dasabuvir) indirectly block RNA replication. Nuceotide analogues (sofobuvir) lead to chain termination after being incorporated into newly synthesized viral RNA.
From these four groups come the three current strategies for HCV treatment, and Dr. Pawlotsky said he didn’t see many new treatments on the horizon.
The first strategy uses a nucleotide analogue with a high barrier to resistance that serves as the backbone of treatment with one of the drugs that has a low resistance barrier, either a protease inhibitor or an NS5A inhibitor such as ledipasvir or declatasvir.
The second option combines three drugs with low barriers to resistance — protease inhibitor, NS5A inhibitor and non-nucleoside inhibitor — to increase the barrier to resistance as a group. A current therapeutic example is the combination of paritaprevir, ombitasvir, and desaburvir.
The third strategy involves the use of one second-generation drug that has an improved barrier to resistance in combination with another drug. One such combination, the second-generation protease inhibitor grazoprever with the second-wave NS5A inhibitor elbasvir, should be approved in the coming months, Dr. Pawlotsky said.
The HCV guidance document published this year by AASLD and IDSA along with the EASL document also from 2015 recommends that those with chronic HCV infection should get treatment.
Every patient, Dr. Pawlotsky said, has by basic principle the right to be treated. But both cost of treatment and, more importantly, the number HCV patients mean not everybody can have access to treatment in the next year or two.
“There has been some misunderstanding of the term prioritization,” he said. “When you prioritize patients, you don’t deny therapy to the ones who are not treated immediately. You just say that these other patients need to be treated now. The other ones have the right to be treated, and they will be treated later.”
Despite the recommendation for treatment of nearly all patients with HCV infection, Dr. Pawlotsky said, it remains important for clinicians to understand patient- and disease-related factors that place individuals at risk for HCV-related complications as well as for HCV transmission.
“Implementation is a big issue,” Dr. Pawlotsky said. “Most of us come from countries where medicine is accessible, drugs are reimbursed and covered. This isn’t true everywhere. This disease infects 150 million people worldwide, and we have to, by all means, provide access to these therapies to everybody in the world who is infected. Everybody has a right to be treated.”





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StephenW

www.natap.org

临床医生用于治疗HCV多1线;挑战是实现
发布者：AASLD于：2015年11月15号

http://www.livermeetingtoday.org ... -is-implementation/

发现继承自丙型肝炎病毒（HCV）的发现导致了高于90％，在四分之一世纪感染的治愈率。
pawlotskyPG

让 - 米歇尔·Pawlotsky博士

在AASLD研究生课程进修班的巴黎东大学会议我上周六，让 - 米歇尔·Pawlotsky，医学博士，在亨利Mondor大学医院，在法国，审查现在的四个直接作用的抗病毒（DAA）的药物提供如何将这些药物干扰素（IFN）的三重奏 - 免费使用组合治疗和治愈丙型肝炎。国际准则不再建议使用含有干扰素作为一线疗法治疗。

“尽管有这些选项的相应费用，IFN-免费方案是可用的时候，因为他们的病毒学疗效最好的选择，易用性和耐受性，”Pawlotsky博士说。

NS3-4A蛋白酶抑制剂（第一波的telaprevir，用boceprevir;第二波simeprevir，paritaprevir / R，asunaprevir和vaniprevir）关上了病毒的生命周期。 NS5A抑制剂（daclatasvir，ledipasvir，ombitasvir;第二波elbasvir，velpatasvir）瓦解复制复合物，并阻断病毒粒子组装和释放。

非核苷抑制剂（dasabuvir）间接地阻断RNA复制。 Nuceotide类似物（sofobuvir）导致链终止被掺入新合成的病毒RNA后。

从这四组来到三目前的战略丙型肝炎病毒治疗，并Pawlotsky博士说，他没有看到地平线上的许多新的治疗方法。

第一个策略采用具有高耐药屏障用作治疗与具有低电阻屏障的药物之一的主链的核苷酸类似物，无论是蛋白酶抑制剂或NS5A抑制剂，如ledipasvir或declatasvir。

第二个选项结合了三种药门槛低电阻 - 蛋白酶抑制剂，NS5A抑制剂和非核苷抑制剂 - 增加障碍阻力为一组。电流治疗的例子是paritaprevir，ombitasvir和desaburvir的组合。

第三个策略涉及使用一第二代药物，其具有改善的隔离，以抵抗在与另一种药物。一个这样的组合，第二代蛋白酶抑制剂grazoprever与第二波NS5A抑制剂elbasvir，应在未来数月得到批准，Pawlotsky博士说。

通过AASLD和IDSA随着EASL文件还从2015年开始，今年公布的HCV指导文件建议说，有慢性丙型肝炎病毒感染应得到治疗。

每个患者，Pawlotsky博士说，具有通过基本原理的权利来对待。但是，处理成本和，更重要的是，这个数字HCV患者的意思是不是每个人都能获得治疗，在未来一年或两年。

“我们一直在长期优先的一些误解，”他说。 “当你优先考虑的病人，你不否认治疗不立即处理谁的人。你刚才说，这些病人需要立即治疗。其他的人必须被处理的权利，并且它们将在后面进行处理。“

尽管用于治疗的几乎所有患者的HCV感染的建议，Pawlotsky博士说，它对于临床医生要明白，放置个体风险的HCV相关的并发症，以及用于HCV传输患者 - 和疾病相关的因素仍然是重要的。

“执行是一个大问题，”Pawlotsky博士说。 “我们中的大多数都来自国家的药是可访问的，药物报销覆盖。这是不正确的无处不在。本病感染1.5亿人在全球，我们必须这样做，通过各种手段，可以访问这些疗法给大家的是谁感染了世界。每个人都将被处理的权利。“



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