摘要
目前有近2亿人被丙型肝炎病毒感染,其中大约20%具有HCV慢性感染患者会发展为肝硬化。此外,达74%的患者被报道有HCV肝外表现,如混合型冷球蛋白血症、淋巴瘤、风湿病、自身免疫性甲状腺炎、甲状腺功能减退、甲状腺乳头状癌以及2型糖尿病。在理解HCV生命周期和与HCV慢性感染相关的发炎过程(涉及细胞因子和趋化因子的复杂网络)已经取得了一定的进展。在过去的十年针对慢性HCV感染的患者的治疗标准是利巴韦林和聚乙二醇化干扰素-α的联合治疗。然而,干扰素限制了有效性以及与副反应有关。近期,可作为N5SA或聚合酶或蛋白酶的直接抗毒DAAs与利巴韦林和聚乙二醇化干扰素-α相比表现出更短的治疗时间、更好的效果以及耐受性。循环CXCL-10水平和白细胞介素(IL)-28B基因多态性与DAA s或利巴韦林和聚乙二醇化干扰素-α联合的治疗作用相关。新的DAAs能在不同的分子等级靶向HCV杀灭HCV。针对无干扰素治疗应对抵抗性HCV基因型以及不符合条件的患者或者那些对当前的治疗方案无效的患者提供新的治疗方案。目前为理解这些与HCV清除相关的因素已经做出了大量的研究,为了达到治疗的个体化,减少副作用,增加持续的病毒学应答率并阻止疾病的进展。
Current Drug Targets
Title:Editorial: New Therapies, Markers and Therapeutic Targets in HCV Chronic Infection and HCV Extrahepatic Manifestations
Volume: 18 Issue: 7
摘要: More than 180 millions of subjects in the world are infected by Hepatitis C Virus (HCV), and about 20% of them with HCV chronic infection progress to cirrhosis. Furthermore, numerous HCV extrahepatic manifestations have been reported in up to 74% of patients, as mixed cryoglobulinemia, lymphomas, rheumatic disorders, autoimmune thyroiditis, hypothyroidism, papillary thyroid cancer, and type 2 diabetes. Advances in understanding the HCV life cycle, and the inflammatory processes (involving a complex network of cytokines and chemokines) associated with HCV chronic infection, have led to substantial advancements in therapy. The combination of ribavirin and PEGylated interferon-α was the standard of therapy for HCV chronically infected patients in the last decades. However, interferon has limited effectiveness and is associated with severe adverse effects. Recently, direct-acting antivirals (DAAs) that act as inhibitors of N5SA, or polymerase, or protease have been shown to result in shorter duration of therapy, better efficacy and tolerance, with respect to ribavirin and PEGylated interferon-α. Circulating CXCL10 levels, and the interleukin(IL)-28B gene polymorphisms, are associated with the success of the therapy both with DAAs or ribavirin and PEGylated interferon-alpha. New DAAs targeting the HCV at various molecular levels have been developed to eradicate HCV. Moving to interferonfree therapies should offer new treatments for resistant HCV genotypes, and for ineligible patients or patients failing to respond to prior therapies.
Many efforts have been made to understand the factors that are involved with clearance of HCV to personalize the therapy for each patient, with the aim to reduce side effects, increasing the sustained virologic response rate, and to prevent the progression of the disease.Export Options
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Cite this article as:
Editorial: New Therapies, Markers and Therapeutic Targets in HCV Chronic Infection and HCV Extrahepatic Manifestations, Current Drug Targets 2017; 18 (7) . https://dx.doi.org/10.2174/1389450116666151102095708
DOI https://dx.doi.org/10.2174/1389450116666151102095708 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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