标题: Hepatitis: After HCV cure, HBV cure? [打印本页] 作者: 齐欢畅2 时间: 2016-5-27 18:19 标题: Hepatitis: After HCV cure, HBV cure?
Julie Lucifora & Christian Trepo
AffiliationsCorresponding author
Nature Reviews Gastroenterology & Hepatology 12, 376–378 (2015) doi:10.1038/nrgastro.2015.103
Published online 23 June 2015
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Current treatments efficiently control chronic HBV infection but they do not lead to its elimination. Now, Ebert and colleagues have shown that cellular inhibitor of apoptosis proteins (cIAPs) prevent TNF-mediated killing of infected hepatocytes and that cIAP antagonists might lead to HBV cure by promoting death of infected cells.作者: 齐欢畅2 时间: 2016-5-27 18:20
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Birinapant might be an alternative to
already attractive approaches such as T‑cell
therapy or therapeutic vaccine strategies that
also aimed at specifically killing the infected
hepatocytes.8
However, to avoid fulminant
hepatitis, such therapies would ideally require
liver biopsies of patients to ensure that the
number of HBV‑infected hepatocytes (and
so potentially the number of hepatocytes
that will be lost after the treatment) is fairly
low. In addition, such treatments might
not be adapted to the ‘immunotolerant’
phase during which most, if not all, hepatocytes
are possibly infected. Although some
advances have been made,9,10
the search for treatment enabling noncytolytic
elimination of cccDNA is still important to cure
these so‑called immunotolerant patients,
prevent liver damage before it occurs and
thus reduce health‑care costs associated with
complications of chronic hepatitis B.
In conclusion, Ebert and colleagues’
papers3,6 do represent a true breakthrough
and a first step in the development of new
HBV cure therapies. Indeed, the inhibition of
HBsAg production is the key, and precisely
the shortcoming, of existing treatments.
However, the exact mechanism by which this
step is achieved remains to be further studied,
especially in other experimental models, as
all data provided here have been obtained in
only two mouse models in which HBV
replication was induced through a rather artificial
way (hydrodynamic injection of a plasmid
encoding the HBV genome).
These data provided a compelling rationale
for a clinical trial that has recently been
initiated. Indeed, a phase I/IIa clinical trial
(NCT02288208) in Australia and New
Zealand will evaluate the addition of birinapant
in individuals with chronic hepatitis B who are currently receiving antiviral
therapy with either tenofovir or entecavir.
Unfortunately, recruitment of patients
for this study was put on hold because of
neurological adverse effects. However, these
new findings contribute to optimism in the
possibility of full eradication of HBV in
the future.
INSERM U1052, CNRS UMR_5286, Cancer
Research Center of Lyon (CRCL), 151 Cours
Albert Thomas, 69424 Lyon Cedex 03, France
(J.L., C.T.).Correspondence to: C.T. [email protected]
Birinapant可能是一种替代
已经有吸引力的方法，如T细胞
治疗或治疗性疫苗策略，
也瞄准了专门查杀感染
hepatocytes.8
然而，为了避免暴发型
肝炎，这种疗法将理想要求
患者肝脏活组织检查，以确保
乙肝病毒感染的肝细胞的数目（和
肝如此大的潜在数量
将丢失的处理之后）是相当
低。此外，这样的治疗方法可能
不适合于“免疫耐受”
在此期间，大部分，如果不是全部，肝细胞相
被感染的可能。虽然有些
的进步已经作出，9,10-
寻找治疗使noncytolytic
消除cccDNA的仍然是重要的治疗
这些所谓的免疫耐受的患者，
防止肝损害发生之前和
从而减少相关的医疗保健费用
慢性乙型肝炎的并发症
总之，艾伯特和他的同事“
papers3,6做代表的真正突破
并在新发展的第一步
乙肝治疗疗法。事实上，抑制
HBsAg的生产是关键，并精确
缺点现有的治疗方法。
然而，确切的机制，这
步骤实现还有待进一步研究，
特别是在其它实验模型，如
这里提供的所有数据都在获得
只有两个小鼠模型中，HBV
复制是通过一个相当的人工诱导
方法（质粒注射水动力
编码HBV基因组）。
这些数据提供了一个令人信服的理由
用于临床试验，最近一直
启动。事实上，相I / IIa族临床试验
（NCT02288208）在澳大利亚和
新西兰将评估除了birinapant的
与谁正在接受抗病毒治疗慢性乙型肝炎的个体
疗法与替诺福韦或恩替卡韦。
不幸的是，患者的招募
这项研究被搁置的原因
神经系统的不利影响。然而，这些
新发现有助于乐观情绪的
乙肝病毒完全根除的可能性
未来。
INSERM U1052，CNRS UMR_5286，癌症
里昂（CRCL），151康斯研究中心
阿尔伯特·托马斯，69424里昂Cedex的03，法国
（J.L.，C.T）通讯作者：C.T. [email protected]作者: 齐欢畅2 时间: 2016-5-28 00:04
