病毒性肝炎诱发肝细胞癌的分子机制

StephenW

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma
Simmone D'souza  1 , Keith Ck Lau  1 , Carla S Coffin  1 , Trushar R Patel  1
Affiliations
Affiliation

    1
    Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, AB, Canada.

    PMID: 33132633 PMCID: PMC7579760 DOI: 10.3748/wjg.v26.i38.5759

Free PMC article
Abstract

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.

Keywords: Chronic viral infection; Hallmarks of cancer; Hepatitis B virus; Hepatitis C virus; Hepatitis delta virus co-infection; Hepatocellular carcinoma; Molecular mechanisms; Viral hepatitis.

©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

StephenW

病毒性肝炎诱发肝细胞癌的分子机制
Simmone D'souza 1，Keith Ck Lau 1，Carla S Coffin 1，Trushar R Patel 1
隶属关系
联系

    1个
    卡尔加里大学卡明医学院微生物学，免疫学和传染病系，加拿大AB卡尔加里T2N 1N4。

    PMID：33132633 PMCID：PMC7579760 DOI：10.3748 / wjg.v26.i38.5759

免费PMC文章
抽象

病毒性肝炎的慢性感染影响了全世界半数的十亿人，并可能导致肝硬化，癌症和肝衰竭。肝癌是癌症相关死亡率的第三大诱因，其中肝细胞癌（HCC）占所有原发性肝癌的90％。像HCC这样的实体瘤非常复杂，并且具有异质的肿瘤基因组图谱，从而导致诊断和管理的复杂性。乙型肝炎病毒（HBV），丙型肝炎三角洲病毒（HDV）和丙型肝炎病毒（HCV）的慢性感染是HCC的最大病因。由于慢性病毒感染在HCC发生中起重要作用，因此重要的是研究参与HCC发病机制的直接（病毒相关）和间接（免疫相关）机制。 HBV，HCV和HDV使用的驱动肝癌发生的常见机制包括持续的肝脏炎症（抗病毒免疫反应受损），免疫和病毒蛋白介导的氧化应激以及病毒蛋白对细胞信号通路的调节。 DNA整合以促进基因组不稳定是HBV感染的特征，而导致脂肪变性的代谢重编程是由HCV感染驱动的。本综述旨在简要概述HBV，HCV和HDV分子生物学，重点介绍HCC中与病毒相关的致癌机制和常见分子途径，以及HCC的当前治疗方法和新兴治疗方法。

关键字：慢性病毒感染；癌症的标志；乙型肝炎病毒;丙型肝炎病毒；肝炎三角洲病毒共感染；肝细胞癌；分子机制；病毒性肝炎。

©作者2020。由百世登出版集团有限公司出版。保留所有权利。

StephenW

https://www.wjgnet.com/1007-9327/full/v26/i38/5759.htm