乙型肝炎病毒与肝癌发生相关性研究进展

摘要/Abstract

摘要： 原发性肝癌在我国是第4位常见恶性肿瘤,也是第2位肿瘤致死病因,严重威胁人类的健康。肝细胞癌占肝癌死亡病例的75%～85%,HBV感染与肝癌发生、发展密切相关,可通过直接、间接机制促进肝细胞癌的发生、发展。HBV相关病毒因素对肝细胞癌患者的预后和复发同样具有重要预测价值。本文就HBV感染与肝癌的发生相关性及其在肝癌治疗和预后方面的价值进行综述。

关键词: 乙型肝炎病毒, 肝细胞癌, 乙型肝炎病毒X蛋白, 共价闭合环状DNA

耿家宝, 刘倩楠, 熊熙, 于乐成, 赵卫峰. 乙型肝炎病毒与肝癌发生相关性研究进展[J]. 肝脏, 2025, 30(3): 403-407.

/ 推荐

[1] Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study[J]. Lancet Gastroenterol Hepatol, 2023,8(10):879-907.
[2] Péneau C, Imbeaud S, La Bella T, et al. Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma[J]. Gut, 2022,71(3):616-626.
[3] Sung W K, Zheng H, Li S, et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma[J]. Nat Genet, 2012,44(7):765-769.
[4] Tu T, Budzinska M A, Shackel N A, et al. HBV DNA integration: molecular mechanisms and clinical implications[J]. Viruses, 2017,9(4):75.
[5] Chen L, Zhang C, Xue R, et al. Deep whole-genome analysis of 494 hepatocellular carcinomas[J]. Nature, 2024,627(8004):586-593.
[6] Kiyose H, Nakagawa H, Ono A, et al. Comprehensive analysis of full-length transcripts reveals novel splicing abnormalities and oncogenic transcripts in liver cancer[J]. PLoS Genet, 2022,18(8):e1010342.
[7] Sivasudhan E, Blake N, Lu Z, et al. Hepatitis B viral protein HBx and the molecular mechanisms modulating the hallmarks of hepatocellular carcinoma: a comprehensive review[J]. Cells, 2022,11(4):741.
[8] Lefeuvre C, Le Guillou-Guillemette H, Ducancelle A. A pleiotropic role of the hepatitis b virus core protein in hepatocarcinogenesis[J]. Int J Mol Sci, 2021,22(24):13651.
[9] Liu W, Cai S, Pu R, et al. HBV preS mutations promote hepatocarcinogenesis by inducing endoplasmic reticulum stress and upregulating inflammatory signaling[J]. Cancers (Basel), 2022,14(13):3274.
[10] Liang Y J, Teng W, Chen C L, et al. Clinical implications of HBV PreS/S mutations and the effects of PreS2 deletion on mitochondria, liver fibrosis, and cancer development[J]. Hepatology, 2021,74(2):641-655.
[11] Shoraka S, Hosseinian S M, Hasibi A, et al. The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways[J]. Front Microbiol, 2023,14:1213145.
[12] Lefeuvre C, Roux M, Blanchard S, et al. Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants[J]. Sci Rep, 2022,12(1):10261.
[13] Yang D, Zou J, Guan G, et al. The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome[J]. J Med Virol, 2023,95(10):e29129.
[14] D'Souza S, Lau K C, Coffin C S, et al. Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma[J]. World J Gastroenterol, 2020,26(38):5759-5783.
[15] Elizalde M M, Tadey L, Mammana L, et al. Biological characterization of hepatitis B virus genotypes: their role in viral replication and antigen expression[J]. Front Microbiol, 2021,12:758613.
[16] Tsushima K, Tsuge M, Hiraga N, et al. Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice[J]. J Gastroenterol, 2019,54(7):650-659.
[17] Lin Y, Gao Z X, Shen X, et al. Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-nave patients: a case-control study in a Han Chinese population[J]. BMC Infect Dis, 2018,18(1):28.
[18] Chen Y, Yang X, Chen Y, et al. Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma[J]. BMC Cancer, 2021,21(1):615.
[19] Liu Y, Wu Q, Zhang F, et al. Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease[J]. Cancer Cell Int, 2023,23(1):72.
[20] 李莹,廖宇圣,孙圣斌,等. 血清IL-17与IL-17-197A/G位点单核苷酸多态性和乙型病毒性肝炎易感性研究[J].中华医院感染学杂志, 2020, 30(11): 1647-1650.
[21] Zeng Z, Liu H, Xu H, et al. Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression[J]. BMC Med Genomics, 2021,14(1):84.
[22] Sekiba K, Otsuka M, Funato K, et al. HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA[J]. J Hepatol, 2022,76(1):53-62.
[23] Kusunoki H, Sakamoto T, Kobayashi N, et al. Structural insights into the interaction between the C-terminal-deleted BH3-like motif peptide of hepatitis B virus X protein and Bcl-x(L)[J]. Biochemistry, 2024,63(5):632-643.
[24] Naully P G, Tan M I, Agustiningsih A, et al. cccDNA epigenetic regulator as target for therapeutical vaccine development against hepatitis B[J]. Ann Hepatol, 2024,30(1):101533.
[25] Liu W, Yao Q, Su X, et al. Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome[J]. Nat Commun, 2023,14(1):4663.
[26] Lei Y, Xu X, Liu H, et al. HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G(1)/S cycle[J]. Autophagy, 2021,17(12):4423-4441.
[27] Li Y, Wang F, Geng Z, et al. HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma[J]. Cell Biosci, 2024,14(1):116.
[28] Ling L R, Zheng D H, Zhang Z Y, et al. Effect of HBx on inflammation and mitochondrial oxidative stress in mouse hepatocytes[J]. Oncol Lett, 2020,19(4):2861-2869.
[29] Yen C J, Lin Y J, Yen C S, et al. Hepatitis B virus X protein upregulates mTOR signaling through IKKβ to increase cell proliferation and VEGF production in hepatocellular carcinoma[J]. PLoS One, 2012,7(7):e41931.
[30] Yan W, Rao D, Fan F, et al. Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma[J]. Front Oncol, 2024,14:1407434.
[31] Bertoletti A, Kennedy P T F, and Durantel D. HBV infection and HCC: the 'dangerous liaisons'[J]. Gut, 2018,67(5):787-788.
[32] Khan M, Arooj S, and Wang H. NK cell-based immune checkpoint inhibition[J]. Front Immunol, 2020,11:167.
[33] Yu L, Sun L, Liu X, et al. The imbalance between NKG2A and NKG2D expression is involved in NK cell immunosuppression and tumor progression of patients with hepatitis B virus-related hepatocellular carcinoma[J]. Hepatol Res, 2023,53(5):417-431.
[34] Yu L, Liu X, Wang X, et al. TIGIT(+) TIM-3(+) NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus-related hepatocellular carcinoma[J]. Oncoimmunology, 2021,10(1):1942673.
[35] Gehring A J and Protzer U. Targeting innate and adaptive immune responses to cure chronic HBV infection[J]. Gastroenterology, 2019,156(2):325-337.
[36] Song A, Wang X, Lu J, et al. Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: a meta-analysis[J]. J Viral Hepat, 2021,28(4):601-612.
[37] Yip T C, Wong V W, Tse Y K, et al. Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue-induced hepatitis B surface antigen loss[J]. Aliment Pharmacol Ther, 2021,53(2):321-331.
[38] Li H, Lu D, Chen J, et al. Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China[J]. Int J Surg, 2024,110(4):2263-2274.
[39] Ding W B, Wang M C, Yu J, et al. HBV/Pregenomic RNA increases the stemness and promotes the development of HBV-related HCC through reciprocal regulation with insulin-like growth factor 2 mRNA-binding protein 3[J]. Hepatology, 2021,74(3):1480-1495.
[40] Hsieh Y C, Pan M H, Jeng W J, et al. Serum HBcrAg and hepatocellular carcinoma in a taiwanese population seronegative for HBsAg and anti-HCV[J]. Clin Gastroenterol Hepatol, 2023,21(5):1303-1313.e11.
[41] Chang K C, Lin M T, Wang J H, et al. HBcrAg predicts hepatocellular carcinoma development in chronic B hepatitis related liver cirrhosis patients undergoing long-term effective anti-viral[J]. Viruses, 2022,14(12):2671.
[42] Jeng W J, Papatheodoridis G V, Lok A S F. Hepatitis B[J]. Lancet, 2023,401(10381):1039-1052.
[43] Chiang C J, Yang Y W, You S L, et al. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan[J]. JAMA, 2013,310(9):974-976.
[44] Wong G L, Hui V W, Yip T C, et al. Universal HBV vaccination dramatically reduces the prevalence of HBV infection and incidence of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2022,56(5):869-877.
[45] Qu C, Chen T, Fan C, et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial[J]. PLoS Med, 2014,11(12):e1001774.

乙型肝炎病毒与肝癌发生相关性研究进展

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	康娅, 马金鑫. aMAP评分联合肝硬度值对乙型肝炎肝硬化相关肝细胞癌的预测价值[J]. 肝脏, 2025, 30(3): 343-346.
[2]	程晓洁, 彭星华, 葛海江, 程海超, 张明, 李智峰. 3D肝脏分析软件在复杂型肝细胞癌切除术中的应用[J]. 肝脏, 2025, 30(3): 352-355.
[3]	王军委, 张小龙, 李岩, 刘峥, 张继光, 岳亚玲. miR-490-3p、miR-503-5p在肝细胞癌组织中的表达及与临床病理特征和预后的关系[J]. 肝脏, 2025, 30(3): 356-360.
[4]	农耀斌, 黄鸿娜, 黄晶晶, 杨树栋, 董芷辛, 陈绮华, 周伟. 间充质干细胞与免疫调节关系及其在肝癌治疗中的意义和潜在价值[J]. 肝脏, 2025, 30(3): 398-402.
[5]	刘文明, 张秋秋, 鄢和新. 浅析肝前体细胞对肝癌调控研究[J]. 肝脏, 2025, 30(2): 149-150.
[6]	彭敏, 阚君泽, 高卉, 阚晓. 针对HBV RNA优化的慢性乙型肝炎临床治疗的效果评价[J]. 肝脏, 2025, 30(2): 170-174.
[7]	鲁石, 张志红, 欧阳慧, 贺宇. 血清HBV pgRNA、HBcrAg动态变化对停用NAs治疗的慢性乙型肝炎患者临床和病毒学复发的评估[J]. 肝脏, 2025, 30(2): 175-179.
[8]	王倩, 梁爽, 李静, 徐佳琪, 王方旭. 超声造影结合AFP、SAA/CRP水平在肝细胞腺瘤及肝细胞癌鉴别诊断中的应用[J]. 肝脏, 2025, 30(2): 211-215.
[9]	李云华, 高鑫阳. 普美显肝胆期甜甜圈结节MRI表现联合DCE-MRI灌注定量参数评估肝细胞癌经肝动脉化疗栓塞疗效的价值[J]. 肝脏, 2025, 30(2): 216-221.
[10]	罗晓卫, 周利江, 徐冲. 肝细胞癌发生肺转移的危险因素和血清学指标的评估价值[J]. 肝脏, 2025, 30(2): 226-230.
[11]	朱鹏, 彭明珠, 吴莉莉, 郭世民. 循环肿瘤DNA在肝细胞癌中的临床应用研究进展[J]. 肝脏, 2025, 30(2): 268-271.
[12]	张冬青, 廖资渊, 林升龙, 吴雯军, 王香梅, 马华皙, 高海兵. 双重血浆分子吸附系统在HBV相关慢加急性肝衰竭患者中的疗效分析[J]. 肝脏, 2025, 30(1): 24-30.
[13]	蒋程程, 董鑫园. 细胞角蛋白-19、CA50联合甲胎蛋白对肝细胞癌的疾病进展评估价值[J]. 肝脏, 2025, 30(1): 50-54.
[14]	孟纯, 周文娟, 沈预程. TGF-β1、Ca²⁺和BALP联合检测对HCC骨转移患者的评估价值[J]. 肝脏, 2025, 30(1): 55-60.
[15]	冯加其, 刘雄青, 黄鑫昱, 刘璐, 王甘露. 酒精相关肝细胞癌发生和发展的研究进展[J]. 肝脏, 2025, 30(1): 132-135.