肝细胞癌（HCC）给全球带来了巨大的健康负担，是全球第五大流行癌症。丙型肝炎病毒（HCV）感染仍然是肝癌发生的主要危险因素之一。 HCC是一种异质性疾病，HCV引起的HCC的发生过程错综复杂，涉及多种因素，包括遗传易感性、病毒因素、慢性炎症引起的免疫反应、酗酒以及脂肪肝相关的代谢功能障碍。在这篇综述中，我们对与 HCV 感染相关的 HCC 发生过程中涉及的遗传学和表观遗传机制的研究进行了全面和最新的综述。我们还讨论了潜在的转化意义，包括新的生物标志物和治疗药物。2023 年 6 月在 PubMed 和 Embase 数据库中进行了全面的文献检索。最近的研究结果表明，多种遗传和表观遗传过程参与了发病机制，并继续即使丙型肝炎病毒完全消除后仍然存在。表观基因组的失调已被确定为肝脏疾病有害影响的一个重要因素，特别是在遗传改变不常见的初始阶段。基因表达的持久“表观遗传记忆”被认为受到表观遗传机制的调节，这表明丙型肝炎病毒感染引起的改变仍然存在，并且即使在成功治疗后也与发生肝癌的风险有关。需要系统生物学分析方法来描述肿瘤进化中遗传和表观基因组改变的程度和重要性。通过促进对这些方面更深刻的理解，这最终将促进新疗法的进步并最终改善患者的治疗结果。2024肝胆外科和营养。版权所有。

Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment.A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.2024 Hepatobiliary Surgery and Nutrition. All rights reserved.