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丙型肝炎病毒慢性感染和致癌潜能:疫苗研发进展。

Hepatitis C virus chronicity and oncogenic potential: Vaccine development progress.

机构信息

Department of Internal Medicine, Saint Louis University, Missouri, MO, 63104, USA.

Department of Internal Medicine, Saint Louis University, Missouri, MO, 63104, USA; Department Molecular Microbiology & Immunology, Saint Louis University, Missouri, MO, 63104, USA.

出版信息

Mol Aspects Med. 2024 Oct;99:101305. doi: 10.1016/j.mam.2024.101305. Epub 2024 Aug 20.

Abstract

Hepatitis C virus (HCV) infection is a major health problem worldwide. It can cause liver cirrhosis and hepatocellular carcinoma (HCC), making it a cause of morbidity from liver disease. Thus, there is an urgent need for a prophylactic HCV vaccine. Fortunately, modern medicine has transformed the therapy for HCV infection through development of direct-acting antiviral agents (DAAs), achieving high rates of sustained virologic response and giving significant relief from HCC and associated mortality, but unfortunately it fails to eradicate the risk of HCC, especially in HCV-cleared patients with already advanced liver disease. Additionally, DAA-cured patients do not develop sufficient antiviral immunity and are susceptible to reinfection. A comprehensive strategy to control HCV infection must include a vaccine development approach in which the host can develop humoral and cellular immunity to eradicate HCV successfully; however, this remains a challenge as HCV has developed systems to evade immune attacks from its host. This review highlights the current understanding of HCV's effect on liver disease and cancer progression, the nature of immune responses from cell populations interacting with HCV, and the current strategies for vaccine development. The information in this review will advance prophylactic intervention strategies for HCV infection, with the end goal being to prevent chronicity and subsequent liver disease leading to HCC.

摘要

丙型肝炎病毒 (HCV) 感染是全球范围内的一个主要健康问题。它可导致肝硬化和肝细胞癌 (HCC),从而成为肝脏疾病发病率的一个原因。因此,迫切需要预防性 HCV 疫苗。幸运的是,现代医学通过直接作用抗病毒药物 (DAA) 的开发改变了 HCV 感染的治疗方法,实现了高持续病毒学应答率,并大大减轻了 HCC 及其相关死亡率,但不幸的是,它未能消除 HCC 的风险,尤其是在已经患有晚期肝病的 HCV 清除患者中。此外,DAA 治愈的患者不会产生足够的抗病毒免疫力,并且容易再次感染。控制 HCV 感染的综合策略必须包括疫苗开发方法,在这种方法中,宿主可以产生体液和细胞免疫来成功清除 HCV;然而,这仍然是一个挑战,因为 HCV 已经开发出了逃避其宿主免疫攻击的系统。这篇综述强调了目前对 HCV 对肝病和癌症进展的影响、与 HCV 相互作用的细胞群体的免疫反应的性质以及疫苗开发的当前策略的理解。本综述中的信息将推进 HCV 感染的预防性干预策略,最终目标是预防慢性化和随后导致 HCC 的肝脏疾病。

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