乙型肝炎病毒基因组整合的研究进展

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DOI：10.12449/JCH260104

关键词：慢性乙型肝炎；HBVDNA整合；癌，肝细胞

Abstract：HBVDNAintegration（iDNA）isthecorebarier thatmustbeovercome toachieve functionalcure forchronichepatitis B（CHB）and to prevent the occurrence of hepatocellular carcinoma（HCC）. During reverse transcription， 5%-10% of viral genomes areconvertedintodouble-strandedlinearDNAthatisrandomlyinsertedinto hostchromosomes，generatingstable DNA andcontinuouslyproducing HBsAg，therebydrivingB-andT-cellimmuneexhaustionandlockingthehost inan immune-tolerant state.Theprocessof iDNArunsthroughouttheentirenatural historyofHBVinfection，andtheviralenhancers itcarrescan promoteclonalhyperplasiaofindeterminate potential，accumulatepre-neoplastic mutations，andultimatelyleadtoHCC.Although long-termnucleos（t）ideanalogorinterferon therapycansuppressviralreplicationandreducetheformationofnewintegrations， existingtherapisstilfiltoliminateeistingiDA.Terefore，ereisanurgntndfoiovativestrategistatcanecisely targetintegrationbreakpoints，epigeneticallysilenceiDNA，oreradicateintegratedclones，soastosignificantlyincreasethe functional cure rate of CHB and fundamentallyreduce the risk ofHCC.

Key Words： Chronic Hepatitis B；HBV DNA Integration;Carcinoma，Hepatocellular

Research funding：NationalNatural Science Foundationof China（82361148722）；National Key ResearchandDevelopment Programof China（2023YFC2308600，2024YFE0213800）；Natural Science Foundation for Self-ExplorationResearchof Jilin Province（YDZJ202401427ZYTS）;Jilin Provincial KeyLaboratoryofMetabolic LiverDiseases（YDZJ202502CXJD002）;Program of Jilin Health Talents（JLSWSRCZX2025-098）

乙型肝炎病毒（hepatitisBvirus，HBV）感染仍是全球公共卫生面临的重大挑战，我国慢性HBV感染者约占全球总量的1/3。（剩余10232字）