慢性丙型肝炎病毒感染（HCV）会导致肝脏炎症和纤维化，导致严重的肝脏疾病，例如肝硬化或肝细胞癌（HCC）。直接作用抗病毒药物组合的批准彻底改变了慢性 HCV 治疗，超过 98% 的治疗患者的病毒被根除。这些治疗的功效使得治愈的患者有可能携带先前感染的细胞，这些细胞表现出由慢性丙型肝炎病毒感染直接引起的不可逆转录改变。结合两种不同持续感染模型的差异转录组，我们观察到感染完全消除后感染相关转录本发生了重大逆转。然而，少数转录本在先前感染的细胞中异常表达。增殖和生长停滞细胞培养模型中获得的结果的比较表明，永久性转录改变可能是通过多种机制建立的。有趣的是，在病毒学治愈患者的肝活检中也观察到了其中一些变化。总体而言，我们的数据表明，即使在病毒消除后，持续的 HCV 感染也会对宿主细胞转录组产生直接和永久的影响，可能导致 HCC 的发展。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。

Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct-acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.