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在直接作用抗病毒药物时代,基于他汀类药物(3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂)治疗丙型肝炎病毒(HCV)感染相关疾病

Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents.

作者信息

Kishta Sara Sobhy, Kishta Sobhy Ahmed, El-Shenawy Reem

机构信息

Medical Biotechnology Lab, Microbial Biotechnology Department, National Research Center, Egypt, Cairo, Egypt.

Department of Surgery, Theodor Bilharz Research Institute, Giza, Egypt.

出版信息

F1000Res. 2016 Feb 26;5:223. doi: 10.12688/f1000research.7970.3. eCollection 2016.

Abstract

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs ( , sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

摘要

随着直接抗病毒药物(DAAs)的引入,丙型肝炎病毒(HCV)感染的治疗最近有了进展。然而,尽管病毒成功清除,但许多患者仍有HCV相关疾病进展。因此,必须开发新的治疗方法以实现病毒清除并预防HCV相关疾病的风险。特别是,匹伐他汀与DAAs联合使用可能会提高抗病毒疗效,并降低肝纤维化进展以及HCV相关肝细胞癌的发生率。为了研究使用匹伐他汀和DAAs治疗HCV相关疾病的管理方法,应进行临床试验。然而,人们对他汀类药物与DAAs之间潜在的药物相互作用提出了担忧。因此,应使用复制子系统、人诱导多能干细胞来源的人肝细胞样细胞、人神经元和人心肌细胞进行临床前试验。基于这些临床前试验,可以选择一种最佳的直接抗病毒药物与匹伐他汀和DAAs联合使用。在临床前试验之后,应根据对HCV感染、HCV相关疾病的抗病毒效果和成本效益,将匹伐他汀与最佳直接抗病毒药物的联合用药与其他DAAs联合用药(如索磷布韦和维帕他韦)进行比较。

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