Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis.
Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis.
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DOI：
10.1101/cshperspect.a037366
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发表时间：
2019-09
影响因子：
5.4
通讯作者：
A. Virzì;Armando Andres Roca Suarez;T. Baumert;J. Lupberger
中科院分区：
文献类型：
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作者：
A. Virzì;Armando Andres Roca Suarez;T. Baumert;J. Lupberger
丙型肝炎病毒（HCV）是包括代谢性疾病、纤维化、肝硬化和肝细胞癌（HCC）的肝脏疾病的主要原因。丙型肝炎病毒通过扰乱促炎细胞微环境中的一系列生存、增殖和代谢途径来诱导和促进肝脏疾病进展。使用直接作用抗病毒药物（DAA）的抗病毒治疗最近取得了突破，可以治愈>90%的HCV患者。然而，病毒治疗不能完全消除HCC风险，特别是在晚期肝病或合并症患者中。HCV诱导表观遗传病毒足迹，促进促癌肝特征，其在DAA治愈后持续存在。本文就HCV感染引起的主要信号通路失调及其对肝脏发病机制的影响进行综述。HCV诱导的持续性信号模式可作为HCV治愈的HCC高危患者分层的生物标志物。此外，这些信号通路是新的化学预防策略的潜在目标。
Hepatitis C virus (HCV) is a major cause of liver disease including metabolic disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCV induces and promotes liver disease progression by perturbing a range of survival, proliferative, and metabolic pathways within the proinflammatory cellular microenvironment. The recent breakthrough in antiviral therapy using direct-acting antivirals (DAAs) can cure >90% of HCV patients. However, viral cure cannot fully eliminate the HCC risk, especially in patients with advanced liver disease or comorbidities. HCV induces an epigenetic viral footprint that promotes a pro-oncogenic hepatic signature, which persists after DAA cure. In this review, we summarize the main signaling pathways deregulated by HCV infection, with potential impact on liver pathogenesis. HCV-induced persistent signaling patterns may serve as biomarkers for the stratification of HCV-cured patients at high risk of developing HCC. Moreover, these signaling pathways are potential targets for novel chemopreventive strategies.