• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

整合型乙肝病毒DNA对肿瘤发生及抗病毒治疗的影响。

The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.

作者信息

Zhang Mingming, Chen Han, Liu Huan, Tang Hong

机构信息

Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China.

Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China.

出版信息

Biomark Res. 2024 Aug 15;12(1):84. doi: 10.1186/s40364-024-00611-y.

DOI:10.1186/s40364-024-00611-y
PMID:39148134
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11328401/
Abstract

The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.

摘要

乙肝病毒（HBV）感染的全球负担仍然很高，慢性乙型肝炎（CHB）患者发展为肝硬化和肝细胞癌（HCC）的风险显著增加。抗病毒治疗的最终目标是实现对HBV的清除性治愈。这需要消除肝内共价闭合环状DNA（cccDNA）并彻底根除整合的HBV DNA。本综述旨在总结HBV整合的致癌作用以及在清除性治愈中清除HBV整合的意义。它特别关注HBV整合导致HCC的分子机制，包括原癌基因和肿瘤抑制基因表达的调节、染色体不稳定性的诱导以及截短突变HBV蛋白的表达。该综述还强调了抗病毒治疗在减少HBV整合和预防HBV相关HCC方面的影响。此外，该综述还提供了对CHB治疗未来目标的见解。目前抑制和消除HBV DNA整合的策略主要包括抗病毒治疗、RNA干扰和基因编辑技术。总体而言，HBV整合值得进一步研究，并有可能作为CHB和HBV相关HCC的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/6987cbc5e5d3/40364_2024_611_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/e7a3276f8b19/40364_2024_611_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/56e513afd9ae/40364_2024_611_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/6987cbc5e5d3/40364_2024_611_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/e7a3276f8b19/40364_2024_611_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/56e513afd9ae/40364_2024_611_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6ff/11328401/6987cbc5e5d3/40364_2024_611_Fig3_HTML.jpg

相似文献

1
The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.整合型乙肝病毒DNA对肿瘤发生及抗病毒治疗的影响。
Biomark Res. 2024 Aug 15;12(1):84. doi: 10.1186/s40364-024-00611-y.
2
Current Status and Challenges in Anti-Hepatitis B Virus Agents Based on Inactivation/Inhibition or Elimination of Hepatitis B Virus Covalently Closed Circular DNA.基于乙型肝炎病毒共价闭合环状 DNA 的失活/抑制或清除的抗乙型肝炎病毒药物的现状与挑战。
Viruses. 2023 Nov 25;15(12):2315. doi: 10.3390/v15122315.
3
Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure.功能性治愈的慢性乙型肝炎患者肝内共价闭合环状DNA的减少及乙肝病毒整合情况
J Clin Transl Hepatol. 2023 Apr 28;11(2):314-322. doi: 10.14218/JCTH.2022.00177. Epub 2022 Jul 19.
4
Among Patients with Undetectable Hepatitis B Surface Antigen and Hepatocellular Carcinoma, a High Proportion Has Integration of HBV DNA into Hepatocyte DNA and No Cirrhosis.在乙型肝炎表面抗原检测不到的肝癌患者中，很大一部分存在 HBV DNA 整合到肝细胞 DNA 中而无肝硬化。
Clin Gastroenterol Hepatol. 2020 Feb;18(2):449-456. doi: 10.1016/j.cgh.2019.06.029. Epub 2019 Jun 25.
5
Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B.全外显子 HBV DNA 整合与 HBeAg 阴性慢性乙型肝炎的肝内 HBV 储库无关。
Gut. 2021 Dec;70(12):2337-2348. doi: 10.1136/gutjnl-2020-323300. Epub 2020 Dec 21.
6
Reduced Expression of DNA Damage Repair Genes High Mobility Group Box1 and Poly(ADP-ribose) Polymerase1 in Inactive Carriers of Hepatitis B Virus Infection-A Possible Stage of Viral Integration.乙肝病毒感染非活动携带者中DNA损伤修复基因高迁移率族蛋白盒1和聚（ADP-核糖）聚合酶1表达降低——病毒整合的一个可能阶段
J Clin Exp Hepatol. 2013 Jun;3(2):89-95. doi: 10.1016/j.jceh.2013.04.003. Epub 2013 May 22.
7
Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.尽管抗乙型肝炎病毒治疗和肿瘤消融成功，但仍存在新发、再发和复发性肝细胞癌的持续风险：治愈乙型肝炎病毒的必要性。
World J Hepatol. 2019 Jan 27;11(1):65-73. doi: 10.4254/wjh.v11.i1.65.
8
Clinical evaluation of hepatitis B core-related antigen in chronic hepatitis B and hepatocellular carcinoma patients.慢性乙型肝炎和肝细胞癌患者中乙型肝炎核心相关抗原的临床评估。
Clin Chim Acta. 2018 Nov;486:237-244. doi: 10.1016/j.cca.2018.07.027. Epub 2018 Jul 17.
9
Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients.血清乙型肝炎核心相关抗原 (HBcrAg) 与慢性乙型肝炎患者共价闭合环状 DNA 转录活性相关。
J Hepatol. 2019 Apr;70(4):615-625. doi: 10.1016/j.jhep.2018.11.030. Epub 2018 Dec 7.
10
Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg-positive patients with functional cure following PEG-IFN-based therapy.基于 PEG-IFN 治疗后实现功能性治愈的 HBsAg 阳性患者肝内，整合的 HBV DNA 和 cccDNA 维持转录活性。
Aliment Pharmacol Ther. 2023 Nov;58(10):1086-1098. doi: 10.1111/apt.17670. Epub 2023 Aug 29.

引用本文的文献

1
Evaluating serum extra spindle pole bodies-like 1 protein p53 antibody for hepatitis B virus-related hepatocellular carcinoma diagnosis.评估血清额外纺锤极体样蛋白1抗体用于乙型肝炎病毒相关肝细胞癌的诊断
World J Hepatol. 2025 Jul 27;17(7):108850. doi: 10.4254/wjh.v17.i7.108850.
2
Historical and Emerging Trends in Hepatitis B Virus Integration: A Bibliometric Visual Analysis.乙型肝炎病毒整合的历史与新趋势：文献计量可视化分析
Hepat Med. 2025 Jul 18;17:39-59. doi: 10.2147/HMER.S526977. eCollection 2025.
3
Viral-Track integrated single-cell RNA-sequencing reveals HBV lymphotropism and immunosuppressive microenvironment in HBV-associated hepatocellular carcinoma.

本文引用的文献

1
Long-term antiviral therapy is associated with changes in the profile of transcriptionally active HBV integration in the livers of patients with CHB.长期抗病毒治疗与慢性乙型肝炎患者肝脏中转录活跃的 HBV 整合特征的变化有关。
J Med Virol. 2024 Jun;96(6):e29606. doi: 10.1002/jmv.29606.
2
Gene-Editing and RNA Interference in Treating Hepatitis B: A Review.基因编辑和 RNA 干扰在乙型肝炎治疗中的应用：综述。
Viruses. 2023 Dec 8;15(12):2395. doi: 10.3390/v15122395.
3
Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss.
Viral-Track整合单细胞RNA测序揭示了乙肝病毒相关肝细胞癌中的乙肝病毒嗜淋巴细胞性和免疫抑制微环境。
Commun Biol. 2025 Jul 9;8(1):1030. doi: 10.1038/s42003-025-08443-8.
4
Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression.关于非编码RNA在乙肝病毒/共价闭合环状DNA驱动的肝癌进展中的观点。
Cancer Cell Int. 2025 Jun 21;25(1):224. doi: 10.1186/s12935-025-03849-0.
5
HBV core protein enhances WDR46 stabilization to upregulate NUSAP1 and promote HCC progression.乙肝病毒核心蛋白增强WDR46稳定性以上调NUSAP1并促进肝癌进展。
Hepatol Commun. 2025 May 6;9(5). doi: 10.1097/HC9.0000000000000680. eCollection 2025 May 1.
6
Diverse potential of chimeric antigen receptor-engineered cell therapy: Beyond cancer.嵌合抗原受体工程细胞疗法的多样潜力：超越癌症。
Clin Transl Med. 2025 Apr;15(4):e70306. doi: 10.1002/ctm2.70306.
7
Projected Mitigation of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B in the Gray Zone and the Immune-Tolerant Phase in the United States.美国慢性乙型肝炎灰色区和免疫耐受期患者肝细胞癌预计缓解情况
Dig Dis Sci. 2025 Apr;70(4):1547-1554. doi: 10.1007/s10620-025-08909-z. Epub 2025 Feb 20.
空间转录组学揭示 HBsAg 丢失患者中转录活跃的乙型肝炎病毒整合程度较低。
Gut. 2024 Apr 5;73(5):797-809. doi: 10.1136/gutjnl-2023-330577.
4
Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg-positive patients with functional cure following PEG-IFN-based therapy.基于 PEG-IFN 治疗后实现功能性治愈的 HBsAg 阳性患者肝内，整合的 HBV DNA 和 cccDNA 维持转录活性。
Aliment Pharmacol Ther. 2023 Nov;58(10):1086-1098. doi: 10.1111/apt.17670. Epub 2023 Aug 29.
5
Multiomics analyses reveal pathological mechanisms of HBV infection and integration in liver cancer.多组学分析揭示了乙型肝炎病毒感染和整合在肝癌中的病理机制。
J Med Virol. 2023 Aug;95(8):e28980. doi: 10.1002/jmv.28980.
6
Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.合成 gRNA/Cas9 核糖核蛋白靶向 HBV DNA 抑制病毒复制。
J Med Virol. 2023 Jul;95(7):e28952. doi: 10.1002/jmv.28952.
7
Mitochondrial DNA is a target of HBV integration.线粒体 DNA 是 HBV 整合的靶点。
Commun Biol. 2023 Jul 3;6(1):684. doi: 10.1038/s42003-023-05017-4.
8
Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma.对乙肝病毒整合位点的重新分析揭示了与肝细胞癌肿瘤发生相关的潜在新基因座。
World J Virol. 2023 Jun 25;12(3):209-220. doi: 10.5501/wjv.v12.i3.209.
9
HBV-integrated local genomic alterations reveal multicentric independent occurrences of multifocal HCC.乙肝病毒整合的局部基因组改变揭示了多灶性肝癌的多中心独立发生情况。
Clin Transl Med. 2023 Jun;13(6):e1313. doi: 10.1002/ctm2.1313.
10
Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference.旨在实现慢性乙型肝炎和丁型肝炎治愈的临床试验治疗终点和研究设计指南：2022 年美国肝病研究学会-欧洲肝脏研究学会乙型肝炎-丁型肝炎治疗终点会议报告。
J Hepatol. 2023 Nov;79(5):1254-1269. doi: 10.1016/j.jhep.2023.06.002. Epub 2023 Jun 21.