Aiming for cure in HBV and HDV infection
Aiming for cure in HBV and HDV infection
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DOI：
10.1016/j.jhep.2016.05.043
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发表时间：
2016-10-01
影响因子：
25.7
通讯作者：
Levrero, Massimo
中科院分区：
文献类型：
--
作者：
Petersen, Joerg;Thompson, Alexander J.;Levrero, Massimo
慢性B型肝炎病毒（HBV）感染仍然是世界范围内的主要健康负担。目前可用于慢性B型肝炎的抗病毒治疗选择包括聚乙二醇化干扰素α 2a（PegIFN）或核苷（酸）类似物（NAs）。NA的主要优点是良好的耐受性和有效的抗病毒活性，与对治疗的高持续治疗应答率相关。聚乙二醇干扰素的优势包括疗程有限，没有耐药性，并有机会获得持久的治疗后反应的治疗。此外，聚乙二醇干扰素是唯一批准的药物，已知对丁型肝炎病毒（HDV）有活性。使用这两种具有不同作用机制的抗病毒药物联合治疗B型肝炎在理论上是一种有吸引力的治疗方法。尽管一些研究已经证实了联合治疗的某些病毒学优势，但缺乏支持患者长期临床获益的数据，PegIFN或NAs单药治疗仍然是首选治疗。此外，采用目前的治疗方法，只有有限数量的患者达到B型肝炎表面抗原（HBsAg）丧失。HBsAg丢失被认为是“功能性治愈”，但并不意味着病毒根除。需要不仅能够抑制病毒复制，而且能够解决HBV感染的新型治疗方法。一个关键的挑战是靶向感染肝细胞核中的共价闭合环状DNA（cccDNA）。创新的体外和体内系统以及敏感的分子技术的最近发展和可用性为研究HBV在感染过程中与宿主建立的复杂相互作用网络以及确定抗病毒策略的新靶点开辟了新的可能性。几种新的抗病毒或免疫调节化合物已经达到临床前或临床测试，目的是沉默或根除cccDNA以实现功能性治愈。这些策略中的许多也可能对HDV的治疗有效，HDV在其生命周期中依赖于HBsAg。本临床试验观察总结了旨在直接靶向病毒B和D或改善慢性HBV感染期间免疫反应的最新治疗策略。(C)2016年欧洲肝脏研究协会。Elsevier B.V.出版，保留所有权利。
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide. Currently available antiviral treatment options for chronic hepatitis B include pegylated interferon alpha2a (PegIFN) or nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of sustained on treatment response to therapy. The advantages of PegIFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post-treatment response to therapy. Furthermore, PegIFN is the only approved agent known to be active against hepatitis D virus (HDV). The use of these two antiviral agents with different mechanisms of action in combination against hepatitis B is theoretically an attractive approach for treatment. Although several studies have confirmed certain virological advantages of combination therapies, data supporting a long-term clinical benefit for patients are lacking and monotherapy with PegIFN or NAs remains the therapy of choice. Moreover, with the current treatment approaches, only a limited number of patients achieve hepatitis B surface antigen (HBsAg) loss. HBsAg loss is considered a "functional cure", but does not mean viral eradication. There is a need for novel therapeutic approaches that enable not only suppression of viral replication, but resolution of HBV infection. A key challenge is to target covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. The recent development and availability of innovative in vitro and in vivo systems and sensitive molecular techniques has opened new possibilities to study the complex network of interactions that HBV establishes with the host in the course of infection and to define new targets for antiviral strategies. Several new antiviral or immunomodulatory compounds have reached preclinical or clinical testing with the aim of silencing or eradicating cccDNA to achieve functional cure. Many of these strategies may also be effective for the treatment of HDV, which is dependent on HBsAg for its life cycle. This Clinical Trial Watch summarizes the most recent therapeutic strategies designed to directly target the viruses B and D or to improve immune responses during chronic HBV infection. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.