Domovitz Tom, Gal-Tanamy Meital
Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
J Clin Med. 2021 Feb 2;10(3):551. doi: 10.3390/jcm10030551.
Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy available, HCV is a curable cancer-associated infectious agent, HCC prevalence is expected to continue to rise because HCC risk still persists after HCV cure. Understanding the factors that lead from HCV infection to HCC pre- and post-cure may open-up opportunities to novel strategies for HCC prevention. Herein, we provide an overview of the reported evidence for the induction of alterations in the transcriptome of host cells via epigenetic dysregulation by HCV infection and describe recent reports linking the residual risk for HCC post-cure with a persistent HCV-induced epigenetic signature. Specifically, we discuss the contribution of the epigenetic changes identified following HCV infection to HCC risk pre- and post-cure, the molecular pathways that are epigenetically altered, the downstream effects on expression of cancer-related genes, the identification of targets to prevent or revert this cancer-inducing epigenetic signature, and the potential contribution of these studies to early prognosis and prevention of HCC as an approach for reducing HCC-related mortality.
丙型肝炎病毒（HCV）是全球范围内导致死亡和发病的主要原因，也是肝细胞癌（HCC）的主要病因。HCV感染以及与HCV相关的肝脏疾病的发病率正在上升。尽管现在有了新的直接作用抗病毒药物（DAA）疗法，HCV成为一种可治愈的与癌症相关的感染因子，但由于HCV治愈后肝癌风险仍然存在，预计HCC患病率将继续上升。了解从HCV感染到治愈前后HCC发生的因素，可能为HCC预防的新策略带来机遇。在此，我们概述了已报道的证据，即HCV感染通过表观遗传失调诱导宿主细胞转录组改变，并描述了最近将治愈后HCC的残留风险与持续的HCV诱导的表观遗传特征联系起来的报道。具体而言，我们讨论了HCV感染后确定的表观遗传变化对治愈前后HCC风险的贡献、表观遗传改变的分子途径、对癌症相关基因表达的下游影响、预防或逆转这种致癌表观遗传特征的靶点识别，以及这些研究对早期预后和预防HCC的潜在贡献，以此作为降低HCC相关死亡率的一种方法。
