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乙型肝炎有治愈方法吗? [复制链接]

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发表于 2022-7-8 14:44 |只看该作者 |倒序浏览 |打印
长而短的答案是,目前还没有治愈乙型肝炎的方法。理解为什么需要深入了解病毒本身以及治愈研究人员面临的挑战。

乙型肝炎是由乙型肝炎病毒(HBV)引起的传染病。虽然大多数暴露于乙型肝炎的人会在感染后很快自发清除病毒(将其从体内清除),但仍有一部分人会继续发展为慢性(持续性)感染。

其中,大约四分之一会出现严重的肝脏并发症,包括肝硬化(肝脏大面积瘢痕形成)和肝癌,通常在初次感染后数年。 3

自从 1966 年美国国立卫生研究院的科学家首次发现乙型肝炎病毒以来,就一直在努力寻找治愈乙型肝炎的方法。4 然而,很快就清楚,在实现真正的治愈之前,需要克服许多障碍。其中最主要的是:

    先天免疫力差:由于尚不完全清楚的原因,HBV 在早期感染期间不易被免疫系统识别,并且很难被机体的前线先天免疫反应消除。 5
    适应性免疫差:随着时间的推移,身体的疾病特异性适应性免疫反应也会因一种称为 T 细胞衰竭的现象而减弱。发生这种情况时,免疫系统识别和发起针对病毒的免疫攻击的能力会降低。 5
    病毒库:在慢性感染者中,HBV 会嵌入肝脏内外的组织内,称为病毒库。在这些宿主中,病毒在很大程度上不受免疫检测的影响,并且很难用抗病毒药物接触到。 6
    cccDNA:乙型肝炎与丙型肝炎的区别在于其病毒 DNA 的独特结构,称为共价闭合环状 DNA (cccDNA)。抗病毒药物对这种看似坚不可摧的“微型染色体”的效果有限,这种“微型染色体”会继续从受感染的肝细胞中排出新病毒。 7

病毒性肝炎如何传播?
克服障碍

尽管在寻找治愈方法方面存在挑战,但科学家们对 HBV 如何感染、复制和持续存在有了更深入的了解。通过使用一种或多种疗法来靶向和阻断这些机制,科学家们希望有一天能够使病毒无害或消除它。

一些领先的候选药物包括:

    Bepirovirsen:一种实验性的直接作用抗病毒药物,可能会阻止 cccDNA 传递用于构建新病毒的遗传密码8
    HBsAg 单克隆抗体:一种免疫疗法的实验形式,用于增强免疫系统识别和发起针对 HBV9 的靶向免疫攻击的能力
    JNJ-64300535:一种实验性治疗性疫苗,可能有助于激活慢性乙型肝炎感染者的适应性免疫反应10
    REP 2139/2165:一种实验性抗病毒直接作用抗病毒药物,似乎可以提高免疫系统控制病毒的能力11
    RO7049389:一种实验性的直接作用抗病毒药物,可阻止新病毒的组装12

临床试验

今天,至少有 50 种不同的 HBV 疗法——包括超过 25 种实验性直接作用抗病毒药物——正在进行临床试验,预计还会有更多。 13

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发表于 2022-7-8 14:44 |只看该作者
Is There a Cure for Hepatitis B?

The long and short answer is that there is not yet a cure for hepatitis B. Understanding why requires insight into the virus itself and the challenges cure researchers face.

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV). While most people exposed to hepatitis B will spontaneously clear the virus (eliminating it from the body) soon after infection, a proportion will go on to develop a chronic (persistent) infection.

Of these, around one in four will develop severe liver complications, including cirrhosis (extensive scarring of the liver) and liver cancer, typically years after the initial infection.3

Efforts to find a cure for hepatitis B have been underway since the virus was first identified by scientists at the National Institutes of Health in 1966.4 It soon became clear, however, that numerous hurdles would need to be overcome before an actual cure could be achieved. Chief among these are:

    Poor innate immunity: For reasons that are not entirely clear, HBV is not readily recognized by the immune system during early-stage infection and is poorly eliminated by the body's frontline innate immune response.5
    Poor adaptive immunity: Over time, the body's disease-specific adaptive immune response also weakens due to a phenomenon known as T-cell exhaustion. When this occurs, the immune system is less able to recognize and launch an immune assault against the virus.5
    Viral reservoirs: In chronically infected people, HBV will embed itself within tissues inside and outside the liver, called viral reservoirs. Within these reservoirs, the virus is largely shielded from immune detection and is difficult to reach with antiviral drugs.6
    cccDNA: What differentiates hepatitis B from hepatitis C is the unique structure of its viral DNA, called covalently closed circular DNA (cccDNA). Antiviral drugs have limited effectiveness against this seemingly indestructible "mini-chromosome" that continues to pump out new viruses from infected liver cells.7

How Is Viral Hepatitis Spread?
Overcoming the Hurdles

Despite the challenges in finding a cure, scientists have a greater understanding of how HBV infects, replicates, and persists. By targeting and blocking these mechanisms with either one or a combination of therapies, scientists hope to one day render the virus harmless or eliminate it.

Among some of the leading drug candidates are:

    Bepirovirsen: An experimental direct-acting antiviral that may block cccDNA from delivering the genetic code used to build new viruses8
    HBsAg monoclonal antibody: An experimental form of immunotherapy used to boost the immune system's ability to recognize and launch a targeted immune attack against HBV9
    JNJ-64300535: An experimental therapeutic vaccine that may help activate the adaptive immune response in people with chronic hepatitis B infection10
    REP 2139/2165: An experimental antiviral direct-acting antiviral that appears to improve the immune system's ability to control the virus11
    RO7049389: An experimental direct-acting antiviral that blocks the assembly of new viruses12

Clinical Trials

Today, there are at least 50 different HBV therapies—including more than 25 experimental direct-acting antivirals—undergoing clinical trials, with more expected to follow.13

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发表于 2022-7-8 14:45 |只看该作者

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发表于 2022-7-9 10:06 |只看该作者
本帖最后由 newchinabok 于 2022-7-9 10:07 编辑

今天下半年只有:vir2218+干挠素48周出数据这一个看点了

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发表于 2022-7-9 18:37 |只看该作者
本帖最后由 lancas 于 2022-7-9 18:48 编辑
newchinabok 发表于 2022-7-9 10:06
今天下半年只有:vir2218+干挠素48周出数据这一个看点了

其实感觉希望真不大~~~条件许可的病友就先试试干扰素好了,边等边看新药~~~GSK赶紧入三期~~~看看会不会有好的数据

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发表于 2022-7-9 19:17 |只看该作者
本帖最后由 newchinabok 于 2022-7-9 19:24 编辑
lancas 发表于 2022-7-9 18:37
其实感觉希望真不大~~~条件许可的病友就先试试干扰素好了,边等边看新药~~~GSK赶紧入三期~~~看看会不会有 ...

24周治好3个,也不知道是vir的作用还是干挠素作用,还是有可行性的,主要治愈率要能提高。其它新药还早,没有看点

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发表于 2022-7-9 20:50 |只看该作者
基本上就是干扰素的作用

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8
发表于 2022-7-9 22:12 |只看该作者
Gsk多少年了,如果好的话。需要藏这么多年?资夲家会放过这个赚钱机会?

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发表于 2022-7-9 22:12 |只看该作者
windu 发表于 2022-7-9 20:50
基本上就是干扰素的作用

正解。。
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