Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease.
Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease.
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2021年的丁型肝炎病毒：一种难治性疾病的病毒学、免疫学和新治疗方法。
DOI：
10.1136/gutjnl-2020-323888
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发表时间：
2021-09
期刊：
影响因子：
24.5
通讯作者：
Lampertico P
中科院分区：
文献类型：
--
作者：
Urban S;Neumann-Haefelin C;Lampertico P
大约5%感染B型肝炎病毒（HBV）的个体同时感染丁型肝炎病毒（HDV）。慢性HBV/HDV合并感染与不利的结局相关，许多患者在5-10年内发展为肝硬化、肝功能衰竭并最终发展为肝细胞癌。近年来，HBV/HDV受体的鉴定以及新型体外和动物感染模型的开发使得对HDV生命周期的研究更加详细，促进了特异性抗病毒药物的开发。在未经治疗和治疗的患者中HDV特异性CD 4+和CD 8 +T细胞表位的表征也允许更精确地理解HDV免疫生物学，并可能为免疫策略铺平道路，以支持即将到来的针对病毒或宿主因素的特异性治疗。在过去的30年里，聚乙二醇干扰素-α一直用于治疗HDV患者，但只有有限的持续反应。在这里，我们描述了新的治疗方案，其作用方式和临床效果。其中，入口抑制剂bulevirtide（原名myrcludex B）于2020年在欧盟（EU）获得有条件上市许可（Hepcludex）。另一种药物，异戊烯化抑制剂洛那法尼，目前正在III期临床试验中进行研究。其他治疗策略旨在靶向B型肝炎表面抗原，包括核酸聚合物REP 2139 Ca。HDV病毒学、免疫学和治疗方面的这些最新进展是使HDV成为一种不太难治疗的病毒的重要步骤，我们将对此进行讨论。
Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.
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影响因子：
5.1
作者：
Bazinet M;Pântea V;Cebotarescu V;Cojuhari L;Jimbei P;Anderson M;Gersch J;Holzmayer V;Elsner C;Krawczyk A;Kuhns MC;Cloherty G;Dittmer U;Vaillant A
通讯作者：
Vaillant A
影响因子：
5.4
作者：
Beilstein, Frauke;Blanchet, Matthieu;Sureau, Camille
通讯作者：
Sureau, Camille
影响因子：
25.7
作者：
Giersch, Katja;Allweiss, Lena;Luetgehetmann, Marc
通讯作者：
Luetgehetmann, Marc
影响因子：
5.4
作者：
Blanchet, Matthieu;Sureau, Camille
通讯作者：
Sureau, Camille
影响因子：
3.9
作者：
Billington, Sarah;Ray, Adrian S.;Unadkat, Jashvant D.
通讯作者：
Unadkat, Jashvant D.