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减少乙型肝炎患者不必要的药物治疗 [复制链接]

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发表于 2018-12-1 11:41 |只看该作者 |倒序浏览 |打印
Reducing unnecessary medication for hepatitis B patients
November 30, 2018, Agency for Science, Technology and Research (A*STAR), Singapore
hepatitis b
Credit: CC0 Public Domain

Not all chronic hepatitis B (HBV) patients require lifelong treatment; but the risks of blindly withdrawing treatment can be severe. However, there's little consensus on which patients can be safely discontinued from treatment, highlighting a clear need for a reliable biomarker of post-treatment HBV suppression. Working towards this goal, a team led by A*STAR and Duke-NUS researcher, Antonio Bertoletti, discovered that patients able to discontinue therapy without relapse share the trait of increased HBV-specific immune T cell response.

More than 400 million people suffer from chronic HBV infection. Unlike acute infection, which survivors can overcome and develop immunity to, chronic sufferers are prone to liver inflammation and are subsequently placed on medication indefinitely to suppress viral replication and minimize liver damage—a considerable financial burden and drug toxicity risk. But recent studies have indicated that the immune systems of some chronic HBV patients can control HBV replication and maintain liver health even after treatment ceases. Despite this, stopping treatment remains a dangerous stab in the dark: "In most patients, withdrawing therapy causes a strong rebound of the HBV replication, carrying a high risk of severe liver damage," says Bertoletti.

To identify predictive biomarkers that can help to select chronic HBV patients who can safely stop antiviral treatment, Bertoletti's team recruited 19 chronic HBV patients and observed them during therapy withdrawal for up to two years. They found that heightened levels of HBV-targeting T cells—especially CD8+ T cells expressing a protein called PD-1—were associated with patient health after medication was withdrawn. Bertoletti's team suggest that PD-1 may promote long-term CD8+ T cell survival and antiviral capabilities in chronic HBV patients.

The team verified their findings in a second cohort of 27 patients treated with a different antiviral therapy. The results confirmed that increased HBV-specific T cells are indicative of a patient's capacity to safely discontinue treatment, offering a biomarker with potential for the clinic.

Further work needs to be done before this discovery can benefit patients widely. Bertoletti's team, publishing their findings in the Journal of Clinical Investigation, note that the complex methodology required to analyze HBV-specific T cells requires specialized knowledge and skills not available in every lab. "We are now trying to develop a quick and easy method to measure HBV-T cells, and an assay that can be performed easily, even in hospitals," says Bertoletti.

More information: Laura Rivino et al. Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI92812

Journal reference: Journal of Clinical Investigation search and more info website

Provided by: Agency for Science, Technology and Research

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发表于 2018-12-1 11:42 |只看该作者
减少乙型肝炎患者不必要的药物治疗
2018年11月30日,新加坡科学技术研究局(A * STAR)
乙型肝炎
图片来源:CC0 Public Domain

并非所有慢性乙型肝炎(HBV)患者都需要终身治疗;但盲目撤回治疗的风险可能很严重。然而,关于哪些患者可以安全地停止治疗几乎没有达成共识,突出显然需要可靠的治疗后HBV抑制生物标志物。为实现这一目标,由A * STAR和Duke-NUS研究员Antonio Bertoletti领导的研究小组发现,能够停止治疗而不复发的患者具有增加HBV特异性免疫T细胞反应的特征。

超过4亿人患有慢性HBV感染。与急性感染不同,幸存者可以克服并发展免疫力,慢性患者容易发生肝脏炎症,随后无限期地停药,以抑制病毒复制并最大限度地减少肝损伤 - 相当大的经济负担和药物毒性风险。但最近的研究表明,一些慢性HBV患者的免疫系统即使在治疗停止后也能控制HBV复制并维持肝脏健康。尽管如此,在黑暗中停止治疗仍然是一个危险的刺痛:“在大多数患者中,退出治疗导致HBV复制的强烈反弹,带来严重肝损伤的高风险,”Bertoletti说。

为了确定可以帮助选择可以安全地停止抗病毒治疗的慢性HBV患者的预测性生物标志物,Bertoletti的团队招募了19名慢性HBV患者,并在停药期间观察他们长达两年。他们发现,高水平的HBV靶向T细胞 - 尤其是表达PD-1蛋白的CD8 + T细胞 - 在服药撤销后与患者的健康状况有关。 Bertoletti的团队建议PD-1可以促进慢性HBV患者的长期CD8 + T细胞存活和抗病毒能力。

该团队在第二组27名接受不同抗病毒治疗的患者中验证了他们的发现。结果证实,增加的HBV特异性T细胞表明患者安全地停止治疗的能力,提供了具有临床潜力的生物标志物。

在此发现可以使患者受益广泛之前,还需要做进一步的工作。 Bertoletti的团队在临床研究杂志上发表他们的研究结果,指出分析HBV特异性T细胞所需的复杂方法需要每个实验室都没有的专业知识和技能。 “我们现在正在努力开发一种快速简便的方法来测量HBV-T细胞,并且即使在医院也可以轻松进行检测,”Bertoletti说。

更多信息:Laura Rivino等。乙型肝炎病毒特异性T细胞与核苷(t)ide-类似物治疗中断时的病毒对照相关,Journal of Clinical Investigation(2018)。 DOI:10.1172 / JCI92812

期刊参考:临床调查杂志搜索和更多信息网站

提供:科学,技术和研究机构

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发表于 2018-12-1 12:14 |只看该作者
好消息。

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4
发表于 2018-12-1 18:54 |只看该作者
这个方向不错
CHB战友交流: 234101235 每天吐槽HBV动态,不断同步TAF咨询

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发表于 2018-12-4 14:33 |只看该作者
看看自已能不能停药  可能停, 就可以周游全世界了.
拉米(5年)耐藥,恩替(7年)耐藥, 2015.10.21服下第1顆替諾的超瘦大三羊,替诺进行时....
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