Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

被引:161
作者
D'souza, Simmone [1 ]
Lau, Keith C. K. [1 ]
Coffin, Carla S. [1 ]
Patel, Trushar R. [1 ,2 ]
机构
[1] Univ Calgary, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 1N4, Canada
[2] Univ Lethbridge, Alberta RNA Res & Training Inst, Dept Chem & Biochem, 4401 Univ Dr West, Lethbridge, AB T1K 3M4, Canada
关键词
Chronic viral infection; Hallmarks of cancer; Hepatocellular carcinoma; Hepatitis B virus; Hepatitis C virus; Hepatitis delta virus co-infection; Molecular mechanisms; Viral hepatitis; VIRUS-X-PROTEIN; GROWTH-FACTOR-BETA; AMINO-ACID SUBSTITUTIONS; B-VIRUS; DELTA-VIRUS; OXIDATIVE STRESS; CORE PROTEIN; TUMOR-SUPPRESSOR; HUMAN LIVER; INTRACELLULAR ACCUMULATION;
D O I
10.3748/wjg.v26.i38.5759
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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收藏
页码:5759 / 5783
页数:25
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