摘要丙型病毒性肝炎是由丙型肝炎病毒(HCV)感染引起的传染病,也是全球重大公共卫生问题之一。HCV具有高度遗传异质性,其基因型/亚型多态性是决定病毒传播演化、致病机制及临床诊疗决策的生物学基础。本文系统检索PubMed、Web of Science、中国知网和万方数据知识服务平台等数据库,纳入并分析近30年内发表的关于HCV基因型/亚型分子流行病学和分型技术进展的相关文献。全球HCV流行呈地域聚集性,以GT1、GT3和GT4基因型为主,我国HCV亚型分布由1b、2a向3a、3b和6a亚型转变。高通量测序及多靶区联合验证技术逐步取代传统PCR/线性探针技术,未来需依托基因型数据构建筛查—确证—治疗—随访的全流程闭环管理体系,为我国达成2030年消除病毒性肝炎战略目标提供依据。
Abstract:Hepatitis C is an infectious disease caused by infection with the hepatitis C virus (HCV) and is one of the major global public health issues. HCV exhibits high genetic heterogeneity, and the polymorphism of its genotypes and subtypes forms the biological basis for viral transmission and evolution, pathogenic mechanisms, and clinical diagnosis and treatment decisions. In this review, relevant literature published in the past 30 years on the molecular epidemiology of HCV genotypes/subtypes and advances in genotyping techniques was systematically retrieved and analyzed from PubMed, Web of Science, CNKI and Wanfang Data Knowledge Service Platform. The global HCV epidemic exhibits spatial-temporal clustering, with genotypes 1 (GT1), 3 (GT3) and 4 (GT4) predominating, whereas the HCV subtype distribution in China has shifted from subtypes 1b and 2a to subtypes 3a, 3b and 6a. High-throughput sequencing and multi-target combined verification techniques are gradually replacing conventional PCR/line probe assays. In the future, genotype data should be utilized to construct a closed-loop management system covering the entire process of screening, confirmation, treatment and follow-up, so as to provide the evidence for achieving China's strategic goal of eliminating viral hepatitis by 2030.
宋芳, 白雪, 李翔, 王培生 综述, 廖秀峰 审校. 丙型肝炎病毒基因型流行特征和分型技术进展[J]. 预防医学, 2026, 38(9): 907-911.
SONG Fang, BAI Xue, LI Xiang, WANG Peisheng, LIAO Xiufeng. Epidemiological characteristics and evolution of genotyping technologies for hepatitis C virus genotypes. Preventive Medicine, 2026, 38(9): 907-911.
[1] Simmonds P,Becher P,Bukh J,et al.ICTV virus taxonomy profile:flaviviridae[J].J Gen Virol,2017,98(1):2-3. [2] 张翠,邱茂锋.HCV抗病毒药物耐药突变检测方法的研究进展[J].分子诊断与治疗杂志,2026,18(3):445-448,452. [3] 陈嵩. 丙型肝炎的病理生理学及抗病毒治疗[J].中华临床医师杂志,2012,6(20):21-23. [4] Spearman C W,Dusheiko G M,Hellard M,et al.Hepatitis C[J].Lancet,2019,394(10207):1451-1466. [5] Magiorkinis G,Magiorkinis E,Paraskevis D,et al.The global spread of hepatitis C virus 1a and 1b:a phylodynamic and phylogeographic analysis[J/OL].PLoS Med,2009,6(12)[2026-09-07].http://doi.org/10.1371/journal.pmed.1000198. [6] Blach S,Zeuzem S,Manns M,et al.Global prevalence and genotype distribution of hepatitis C virus infection in 2015:a modelling study[J].Lancet Gastroenterol Hepatol,2017,2(3):161-176. [7] Markov P V,Pepin J,Frost E,et al.Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa[J].J Gen Virol,2009,90(9):2086-2096. [8] Postigo-Hidalgo I,Magassouba N,Soropogui B,et al.Association of hepatitis C virus genotype 2 spread with historic slave trade and commerce routes in Western Africa[J/OL].Virus Evolution,2022,8(2)[2026-09-07].http://doi.org/10.1093/ve/veac066. [9] Khan A,Tanaka Y,Azam Z,et al.Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan[J].J Med Virol,2009,81(7):1189-1197. [10] Chan A,Patel K,Naggie S.Genotype 3 infection:the last stand of hepatitis C virus[J].Drugs,2017,77(2):131-144. [11] Njouom R,Frost E,Deslandes S,et al.Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic[J].J Gen Virol,2009,90(10):2452-2456. [12] Henquell C,Guglielmini J,Verbeeck J,et al.Evolutionary history of hepatitis C virus genotype 5a in France,a multicenter ANRS study[J].Infect Genet Evol,2011,11(2):496-503. [13] Petruzziello A,Marigliano S,Loquercio G,et al.Global epidemiology of hepatitis C virus infection:an up-date of the distribution and circulation of hepatitis C virus genotypes[J].World J Gastroenterol,2016,22(34):7824-7840. [14] Borgia S M,Hedskog C,Parhy B,et al.Identification of a novel hepatitis C virus genotype from punjab,India:expanding classification of hepatitis C virus into 8 genotypes[J].J Infect Dis,2018,218(11):1722-1729. [15] Wang Y,Okamoto H,Tsuda F,et al.Prevalence,genotypes,and an isolate(HC-C2)of hepatitis C virus in Chinese patients with liver disease[J].J Med Virol,1993,40(3):254-260. [16] Du G P,Li X S,Musa T H,et al.The nationwide distribution and trends of hepatitis C virus genotypes in mainland China[J].J Med Virol,2019,91(3):401-410. [17] 张海莹,饶慧瑛,陈红松.中国丙型肝炎病毒感染的现状及清除进程[J].临床肝胆病杂志,2024,40(4):649-653. [18] 苏迎盈,刘慧鑫,汪宁.中国丙型肝炎病毒基因型分布[J].中华流行病学杂志,2013,34(1):80-84. [19] 聂滨,张开炯,刘靳波,等.中国丙型肝炎病毒基因型分布回顾及Meta分析[J].检验医学与临床,2016,13(20):2876-2881. [20] 黄睿,饶慧瑛.“消除”背景下的丙型肝炎病毒感染现状及筛查、诊断对策[J].诊断学理论与实践,2024,23(1):1-8. [21] World Health Organization.Guidance for country validation of viral hepatitis elimination and path to elimination:technical document[EB/OL].[2026-09-07].https://www.who.int/publications/i/item/9789240078635. [22] Pawlotsky J M.Hepatitis C virus genetic variability:pathogenic and clinical implications[J].Clin Liver Dis,2003,7(1):45-66. [23] Hraber P T,Fischer W,Bruno W J,et al.Comparative analysis of hepatitis C virus phylogenies from coding and non-coding regions:the 5' untranslated region(UTR)fails to classify subtypes[J/OL].Virol J,2006,3[2026-09-07].http://doi.org/10.58837/chula.the.2003.727. [24] Smith D B,Bukh J,Kuiken C,et al.Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes:updated criteria and genotype assignment web resource[J].Hepatology,2014,59(1):318-327. [25] Caputo V,Diotti R A,Boeri E,et al.Detection of low-level HCV variants in DAA treated patients:comparison amongst three different NGS data analysis protocols[J/OL].Virol J,2020,17(1)[2026-09-07].http://doi.org/10.1186/s12985-020-01381-3. [26] Manso C F,Bibby D F,Lythgow K,et al.Technical validation of a hepatitis C virus whole genome sequencing assay for detection of genotype and antiviral resistance in the clinical pathway[J/OL].Front Microbiol,2020,11[2026-09-07].http://doi.org/10.3389/fmicb.2020.576572. [27] Lapointe H R,Dong W Y,Dong W W Y,et al.Validation of a genotype-independent hepatitis C virus near-whole genome sequencing assay[J/OL].Viruses,2021,13(9)[2026-09-07].http://doi.org/10.3390/v13091721. [28] Riaz N,Leung P,Barton K,et al.A daptation of oxford nanopore technology for hepatitis C whole genome sequencing and identification of within-host viral variants[J/OL].BMC Genom,2021,22(1)[2026-09-07].http://doi.org/10.1186/s12864-021-07460-1. [29] Baid G,Cook D E,Shafin K,et al.Deep consensus improves the accuracy of sequences with a gap-aware sequence transformer[J].Nat Biotechnol,2023,41(2):232-238. [30] Nieto-Aponte L,Quer J,Ruiz-Ripa A,et al.Assessment of a novel automatic real-time PCR assay on the Cobas 4 800 analyzer as a screening platform for hepatitis C virus genotyping in clinical practice:comparison with massive sequencing[J].J Clin Microbiol,2017,55(2):504-509. [31] Meng S,Li J M.A novel duplex real-time reverse transcriptase-polymerase chain reaction assay for the detection of hepatitis C viral RNA with armored RNA as internal control[J/OL].Virol J,2010,7[2026-09-07].http://doi.org/10.1186/1743-422X-7-117. [32] Stelzl E,Appel H M,Mehta R,et al.Evaluation of the new cobas® HCV genotyping test based on real-time PCRs of three different HCV genome regions[J].Clin Chem Lab Med,2017,55(4):517-521. [33] Yusrina F,Chua C W,Lee C K,et al.Comparison of cobas® HCV GT against Versant HCV genotype 2.0 (LiPA) with confirmation by Sanger sequencing[J].J Virol Methods,2018,255:8-13. [34] Yang R F,Cong X,Du S C,et al.Performance comparison of the versant HCV genotype 2.0 assay(LiPA)and the abbott realtime HCV genotype II assay for detecting hepatitis C virus genotype 6[J].J Clin Microbiol,2014,52(10):3685-3692. [35] Daniel H D,David J,Raghuraman S,et al.Comparison of three different hepatitis C virus genotyping methods:5'NCR PCR-RFLP,core type-specific PCR,and NS5b sequencing in a tertiary care hospital in South India[J/OL].J Clin Lab Anal,2017,31(3)[2026-09-07].http://doi.org/10.1002/jcla.22045/. [36] Warkad S D,Nimse S B,Song K S,et al.HCV detection,discrimination,and genotyping technologies[J/OL].Sensors,2018,18(10)[2026-09-07].http://doi.org/10.3390/s18103423. [37] Bhattacharya D,Aronsohn A,Price J,et al.Hepatitis C guidance 2023 update:American association for the study of liver diseases-infectious diseases society of America recommendations for testing,managing,and treating hepatitis C virus infection[J/OL].Clin Infect Dis,2023,319[2026-09-07].http://doi.org/10.1093/cid/ciad319. [38] Stelzl E,Haas B,Bauer B,et al.First identification of a recombinant form of hepatitis C virus in Austrian patients by full-genome next generation sequencing[J/OL].PLoS One,2017,12(7)[2026-09-07].http://doi.org/10.1371/journal.pone.0181273.