Frericks Nicola, Klöhn Mara, Lange Frauke, Pottkämper Lilli, Carpentier Arnaud, Steinmann Eike
Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between Hannover Medical School (MHH) and Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Antiviral Res. 2025 Feb;234:106062. doi: 10.1016/j.antiviral.2024.106062. Epub 2024 Dec 21.
Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) primarily cause self-limiting acute hepatitis. However, studies have also reported chronic progression of HEV disease in immunocompromised patients. While considerable progress has been made in the treatment of HCV and HBV through the development of direct-acting antivirals (DAAs), challenges including drug resistance, incomplete viral suppression resulting in failure to achieve clearance and the lack of effective treatment options for HDV and HEV remain. Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to DAAs and aim to disrupt virus-host interactions by modulating host cell pathways that are hijacked during the viral replication cycle. The aim of this review is to provide a comprehensive overview about the major milestones in research and development of HTAs for chronic HBV/HDV and HCV infections. It also summarizes the current state of knowledge on promising host-targeting therapeutic options against HEV infection.
感染五种已知肝炎病毒中的一种或几种是肝病的主要病因，慢性感染时发生肝细胞癌的风险很高。慢性感染主要由乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）引起，在全球范围内构成重大的健康负担。慢性HBV感染患者与丁型肝炎病毒（HDV）的合并感染较少见，但被视为慢性病毒性肝炎最严重的形式。甲型肝炎病毒（HAV）和戊型肝炎病毒（HEV）主要引起自限性急性肝炎。然而，研究也报道了免疫功能低下患者中戊型肝炎疾病的慢性进展。虽然通过开发直接作用抗病毒药物（DAA）在丙型肝炎病毒和乙型肝炎病毒的治疗方面取得了相当大的进展，但耐药性、病毒抑制不完全导致无法清除病毒以及缺乏针对丁型肝炎病毒和戊型肝炎病毒的有效治疗方案等挑战仍然存在。靶向宿主的抗病毒药物（HTA）已成为有前景的替代DAA的方法，旨在通过调节病毒复制周期中被劫持的宿主细胞途径来破坏病毒与宿主的相互作用。本综述的目的是全面概述针对慢性HBV/HDV和HCV感染的HTA研发的主要里程碑。它还总结了针对戊型肝炎病毒感染的有前景的靶向宿主治疗选择的当前知识状态。
