Article(id=1321169762713977345, tenantId=1146029695717560320, journalId=1319373219989389464, issueId=1321169668631548508, articleNumber=null, orderNo=null, doi=10.11847/zgggws1147094, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1739376000000, receivedDateStr=2025-02-13, revisedDate=1740326400000, revisedDateStr=2025-02-24, acceptedDate=1755014400000, acceptedDateStr=2025-08-13, onlineDate=1792921017577, onlineDateStr=2026-10-25, pubDate=1757433600000, pubDateStr=2025-09-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792921017577, onlineIssueDateStr=2026-10-25, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792921017577, creator=13701087609, updateTime=1792921017577, updator=13701087609, issue=Issue{id=1321169668631548508, tenantId=1146029695717560320, journalId=1319373219989389464, year='2025', volume='41', issue='9', pageStart='1025', pageEnd='1152', issueExtLink='null', onlineDate='null', pubDate='1757433600000', pubDateStr='2025-09-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792920995147, creator='13701087609', updateTime=1792920995147, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=1074, endPage=1078, ext={EN=ArticleExt(id=1321169762986607106, articleId=1321169762713977345, tenantId=1146029695717560320, journalId=1319373219989389464, language=EN, title=Genotype distribution and drug resistance of hepatitis C virus among 99 intravenous drug users in Guangzhou, columnId=1321169730682077453, journalTitle=Chinese Journal of Public Health, columnName=Special Report — United in the Fight Against Hepatitis C, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the genotype distribution and drug resistance of hepatitis C virus (HCV) among intravenous drug users (IDUs) in Guangzhou. Methods Plasma samples were collected from 99 IDUs diagnosed with HCV infection between August 2023 and January 2024. RNA was extracted, and the non-structural protein 5B (NS5B) region was amplified and sequenced. Phylogenetic trees were constructed via the maximum likelihood method in MEGA11.0.13 software, and the sequences were uploaded to the HCV resistance surveillance database for drug resistance site analysis.

Results

Among the 99 HCV-infected IDUs, 86 were male and 13 were female, with 89.89% (89) of the cases aged over 50 years. A total of 96 NS5B sequences were obtained, revealing four genotypes: 6a, 3a, 1b, and 3b, which accounted for 45.83%, 30.21%, 20.83%, and 3.13%, respectively. The distribution of the four genotypes showed statistically significant differences among male IDUs. All 1b genotype sequences carried the clinically proven drug resistance mutation C316N.

Conclusions

The predominant HCV genotype among IDUs in Guangzhou is 6a, with complex sources of genotype introduction. The prevalence of genotypes differs between male and female IDUs, and middle-aged and elderly IDUs are a key population for HCV infection. Additionally, increased attention should be paid to the drug resistance of the 1b genotype.

, authors=Liyun JIANG, Fanghua LIU, Hao WU, Qingmei LI, Xi CHEN, Zhigang HAN, authorsList=Liyun JIANG, Fanghua LIU, Hao WU, Qingmei LI, Xi CHEN, Zhigang HAN, authorCompany=null, correspAuthors=Zhigang HAN, authorNote=null, correspAuthorsNote=
HAN Zhigang, E-mail:
, copyrightStatement=Copyright © 2025 Chinese Journal of Public Health. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1321169765180228101, articleId=1321169762713977345, tenantId=1146029695717560320, journalId=1319373219989389464, language=CN, title=广州市99例注射吸毒者HCV基因分布及耐药性分析, columnId=1321169730837266703, journalTitle=中国公共卫生, columnName=专题报道——积极行动,共抗丙肝, runingTitle=null, highlight=null, articleAbstract=
目的

了解广东省广州市注射吸毒者(IDUs)感染丙型肝炎病毒(HCV)基因型分布及耐药特征。

方法

2023年8月—2024年1月,收集99例确诊为HCV感染的IDUs血浆样品,提取RNA,对非结构蛋白5B区(NS5B)扩增和测序,使用MEGA11.0.13软件采用最大似然法构建基因进化树,上传HCV耐药监测数据库进行耐药位点分析。

结果

99例IDUs HCV感染者中,男性86例,女性13例,年龄>50岁占89.89%(89例)。测得NS5B序列96条,检出6a、3a、1b和3b基因型4种基因型,分别占45.83%、30.21%、20.83%和3.13%。在男性IDUs中,4种基因型的分布差异有统计学意义。1b基因型序列均检测出耐药突变C316N。

结论

广州市IDUs中HCV感染以6a基因型为主,各基因型的输入来源复杂,男性与女性IDUs中基因型流行情况存在有差别,中老年IDUs是需要关注的HCV感染重点人群,同时需要加强对1b基因型耐药性的关注。

, authors=蒋力云, 刘方华, 吴昊, 黎庆梅, 陈希, 韩志刚*, *, authorsList=蒋力云, 刘方华, 吴昊, 黎庆梅, 陈希, 韩志刚, authorCompany=null, correspAuthors=韩志刚, authorNote=

蒋力云(1980—),主任技师,本科,研究方向:病毒病原学和分子生物学

, correspAuthorsNote=
韩志刚,E-mail:
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蒋力云(1980—),主任技师,本科,研究方向:病毒病原学和分子生物学

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注:图中用△标示参考序列,红色字体的序列为女性IDUs序列。A:6a基因型NS5B基因进化树;B:3a基因型NS5B基因进化树;C:1b基因型NS5B基因进化树;D:3b基因型NS5B基因进化树。

, figureFileSmall=lAtTHUN7Cb0hXb5ix/xFdQ==, figureFileBig=QCzQRfiYDYp3/o/US/kDHg==, tableContent=null), ArticleFig(id=1321169769861071413, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169762713977345, language=EN, label=Tab.1, caption=

Distribution of HCV genotypes among different genders of intravenous drug users

, figureFileSmall=null, figureFileBig=null, tableContent=
基因型男性女性
31~40岁41~50岁51~60岁61~70岁31~40岁41~50岁51~60岁61~70岁
n%n%n%n%n%n%n%n%
HCV-6a00.0055.811719.761922.090017.69215.3800.00
HCV-3a11.1622.321213.951112.790000.00215.3817.69
HCV-1b00.0011.161011.6244.650000.00430.7617.69
HCV-3b00.0000.0022.3200.000000.0017.6900.00
无测序结果00.0000.0011.1611.160000.0017.6900.00
), ArticleFig(id=1321169769944957494, tenantId=1146029695717560320, journalId=1319373219989389464, articleId=1321169762713977345, language=CN, label=表1, caption=

不同性别吸毒人群HCV基因亚型分布(例数,百分比/%)

, figureFileSmall=null, figureFileBig=null, tableContent=
基因型男性女性
31~40岁41~50岁51~60岁61~70岁31~40岁41~50岁51~60岁61~70岁
n%n%n%n%n%n%n%n%
HCV-6a00.0055.811719.761922.090017.69215.3800.00
HCV-3a11.1622.321213.951112.790000.00215.3817.69
HCV-1b00.0011.161011.6244.650000.00430.7617.69
HCV-3b00.0000.0022.3200.000000.0017.6900.00
无测序结果00.0000.0011.1611.160000.0017.6900.00
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广州市99例注射吸毒者HCV基因分布及耐药性分析
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蒋力云 , 刘方华 , 吴昊 , 黎庆梅 , 陈希 , 韩志刚 *, *
中国公共卫生 | 专题报道——积极行动,共抗丙肝 2025,41(9): 1074-1078
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中国公共卫生 |专题报道——积极行动,共抗丙肝 2025 , 41 (9) : 1074 -1078
广州市99例注射吸毒者HCV基因分布及耐药性分析
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蒋力云, 刘方华, 吴昊, 黎庆梅, 陈希, 韩志刚*, *
作者信息
  • 广州市疾病预防控制中心艾滋病预防控制部,广州 510440
通讯作者:
韩志刚,E-mail:
作者简介:

蒋力云(1980—),主任技师,本科,研究方向:病毒病原学和分子生物学

Genotype distribution and drug resistance of hepatitis C virus among 99 intravenous drug users in Guangzhou
Liyun JIANG, Fanghua LIU, Hao WU, Qingmei LI, Xi CHEN, Zhigang HAN
Affiliations
  • Department of AIDS Control and Prevention, Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
  • Corresponding Author:
    HAN Zhigang, E-mail:
出版时间: 2025-09-10 doi: 10.11847/zgggws1147094
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目的

了解广东省广州市注射吸毒者(IDUs)感染丙型肝炎病毒(HCV)基因型分布及耐药特征。

方法

2023年8月—2024年1月,收集99例确诊为HCV感染的IDUs血浆样品,提取RNA,对非结构蛋白5B区(NS5B)扩增和测序,使用MEGA11.0.13软件采用最大似然法构建基因进化树,上传HCV耐药监测数据库进行耐药位点分析。

结果

99例IDUs HCV感染者中,男性86例,女性13例,年龄>50岁占89.89%(89例)。测得NS5B序列96条,检出6a、3a、1b和3b基因型4种基因型,分别占45.83%、30.21%、20.83%和3.13%。在男性IDUs中,4种基因型的分布差异有统计学意义。1b基因型序列均检测出耐药突变C316N。

结论

广州市IDUs中HCV感染以6a基因型为主,各基因型的输入来源复杂,男性与女性IDUs中基因型流行情况存在有差别,中老年IDUs是需要关注的HCV感染重点人群,同时需要加强对1b基因型耐药性的关注。

丙型肝炎病毒  /  非结构蛋白5B区  /  基因型  /  耐药突变  /  注射吸毒者  /  广州市
Objective

To investigate the genotype distribution and drug resistance of hepatitis C virus (HCV) among intravenous drug users (IDUs) in Guangzhou. Methods Plasma samples were collected from 99 IDUs diagnosed with HCV infection between August 2023 and January 2024. RNA was extracted, and the non-structural protein 5B (NS5B) region was amplified and sequenced. Phylogenetic trees were constructed via the maximum likelihood method in MEGA11.0.13 software, and the sequences were uploaded to the HCV resistance surveillance database for drug resistance site analysis.

Results

Among the 99 HCV-infected IDUs, 86 were male and 13 were female, with 89.89% (89) of the cases aged over 50 years. A total of 96 NS5B sequences were obtained, revealing four genotypes: 6a, 3a, 1b, and 3b, which accounted for 45.83%, 30.21%, 20.83%, and 3.13%, respectively. The distribution of the four genotypes showed statistically significant differences among male IDUs. All 1b genotype sequences carried the clinically proven drug resistance mutation C316N.

Conclusions

The predominant HCV genotype among IDUs in Guangzhou is 6a, with complex sources of genotype introduction. The prevalence of genotypes differs between male and female IDUs, and middle-aged and elderly IDUs are a key population for HCV infection. Additionally, increased attention should be paid to the drug resistance of the 1b genotype.

hepatitis C virus (HCV)  /  nonstructual 5B (NS5B) region  /  genotype  /  drug resistance mutation  /  intravenous drug users  /  Guangzhou city
蒋力云, 刘方华, 吴昊, 黎庆梅, 陈希, 韩志刚. 广州市99例注射吸毒者HCV基因分布及耐药性分析. 中国公共卫生, 2025 , 41 (9) : 1074 -1078 . DOI: 10.11847/zgggws1147094
Liyun JIANG, Fanghua LIU, Hao WU, Qingmei LI, Xi CHEN, Zhigang HAN. Genotype distribution and drug resistance of hepatitis C virus among 99 intravenous drug users in Guangzhou[J]. Chinese Journal of Public Health, 2025 , 41 (9) : 1074 -1078 . DOI: 10.11847/zgggws1147094
世界卫生组织(World Health Organization, WHO)统计显示,2022年全球约有5 000万丙型肝炎病毒(hepatitis C virus, HCV)感染者,其中100万人为新感染者;通过对105个国家,1995—2020年的数据分析发现,注射毒品是HCV感染的主要途径之一,占新感染HCV的43.6%;中国因注射毒品造成HCV感染的绝对人数居全球第2[1]。《丙型肝炎防治指南(2022年版)》[2]指出,我国2020年HCV感染者约948.7万例,静脉药瘾共用注射器和不安全注射是目前新发感染HCV最主要的传播方式,注射毒品造成HCV感染的形势不容忽视。泛基因型直接抗病毒治疗药物(direct antiviral agents, DAAs)的使用,对实现WHO实现“2030年消除病毒性肝炎作为公共卫生威胁”的目标具有积极意义。然而,DAAs治疗方案并非适用于所有基因型,需根据当地基因型分布选择合适的治疗策略[2]。掌握HCV基因型的流行情况,选取有效的基因治疗方案,才能保障WHO目标的顺利实现。既往对于广州市注射吸毒者(intravenous drug users, IDUs)感染HCV情况报道较少,本研究通过对该人群感染HCV非结构蛋白5B(nonstructual 5B, NS5B)区进行序列测定,并进行HCV感染基因型研究和耐药突变分析,为本地区规范采取基因型特异治疗方案提供参考,对控制HCV传播和实现公共卫生目标有重要意义。
收集2023年8月—2024年1月在广州医科大学附属第三医院确诊的99例HCV感染的IDUs血浆样本,诊断标准按照《 丙型肝炎诊断:WS213—2018》[3],病例信息来源于中国疾病预防控制信息系统传染病报告信息管理系统。本研究广州市疾病预防控制中心伦理委员会审批(审批编号:GZCDC-ECHR-2025P0001)。
参考文献引物[4],针对HCV的NS5B基因进行扩增,使用PrimeScript™ One Step RT-PCR Kit Ver.2试剂(北京,宝日医生物技术有限公司),反应条件为:50 ℃反转录30 min,94 ℃预变性6 min,94 ℃ 30 s,55 ℃ 30 s,72 ℃ 3 min,扩增循环30次,72 ℃延伸7 min,产物送广州天一辉远公司测序。
测得的NS5B基因序列全部上传至GenBank,并从GenBank中下载参考序列,使用MEGA11.0.13软件采用最大似然法(Maximum Likelihood)构建基因进化树,步长设为1 000,基因型分类参考Simmonds的分类标准[5]。
将测序结果上传到HCV耐药监测数(https://hcv.geno2pheno.org/index.php)[6]进行耐药位点分析。
使用Excel 2010和SPSS 27.0软件进行数据整理和统计分析,计算按照年龄中位数,并按照年龄中位数划分为2个年龄组,计算不同基因型在两个年龄组及男女性别中是否存在显著性差异,P<0.05为差异有统计学意义。
本研究共纳入99例确诊为HCV感染的IDUs,其中男性86例,女性13例,男女比例为6.62:1。年龄范围为39~70岁,年龄中位数为(60.00±5.66)岁,其中>50岁的病例占89.89%(89例)。结果表明,在广州市IDUs中,中老年是感染HCV的主要人群。
成功测得NS5B序列96条(96/99,96.96%),上传至GenBank,序列号为PQ533698–PQ533723,PQ533725–PQ533759,PQ5337761–PQ533795。基因分型结果显示,6 a、3a、1b和3b基因型分别占45.83%(44例)、30.21%(29例)、20.83%(20例)和3.13%(3例),具体分布见表1。以年龄中位数划分为2组,结果显示2组基因型差异无统计学意义(F=3.446,P=0.322)。基因型分布在不同性别中存在显著差异:男性IDUs中,6a基因型的比例显著高于其他基因型(χ2=52.190,P=0.000),而女性IDUs中基因型分布差异无统计学意义(F=3.480,P=0.360)。
将测得的NS5B序列与GenBank中的参考序列比对并构建基因进化树,测得的序列用原始编号和GenBank序列号表示,参考序列以GenBank序列号、国家(地区)、年份和基因亚型表示,女性IDUs序列以红色字体显示。广州市IDUs中6a基因型可以进一步分为分支A和B(图1A),3条女性IDUs序列均归属于分支B。3a基因型与国内既往序列和乌拉圭的序列归属于同一分支(图1B),与美洲、欧洲以及东南亚地区的序列亲缘性较远。1b基因型可分为3个分支,分化度较高(图1C)。3b基因型仅有3条序列,归属于1个分支(图1D)。
在20条1b基因型序列中,均检测出已被临床证实的耐药突变C316N,突变率为100%。其余基因型未检出已被临床证实的耐药突变。
本研究对广州市99例IDUs感染HCV的基因型分布及耐药性进行分析,初步了解了该人群HCV感染的基因型特征及耐药突变情况。广州市IDUs中HCV感染以6a基因型为主,占比45.83%,其次为3a基因型(30.21%)、1b基因型(20.83%)和3b基因型(3.13%)。这一结果与既往广东省IDUs感染HCV的调查结果一致[7],表明6a基因型在广州市IDUs中已成为优势基因型,提示在广州市制定DAAs治疗方案时,应优先考虑对6a基因型有效的药物。
HCV基因型的分布具有明显的地域性差异。本研究结果显示,广州市IDUs中6a基因型的流行率最高,而1b基因型的流行率相对较低,这与全国其他地区的基因型分布有所不同。例如,江苏省、甘肃省和云南省等地的IDUs中,3型基因型(尤其是3 a和3b)占主导地位[8]。广州市作为我国重要的沿海城市,对外贸易和人员交流频繁,6a基因型的流行可能与中国香港、越南等地区的输入有关。通过基因进化树分析,广州市6a基因型序列与中国香港、越南的序列具有较近的亲缘性,进一步支持了这一推测[4, 9–10]。此外,广州市6a基因型序列与加拿大流行的基因序列也有一定的亲缘性,提示不排除为加拿大输入毒株的可能性。3型基因型在IDUs中也较为常见[11],广州市流行的是3a和3b基因型。发达国家以3a基因型流行为主,南亚地区以3a和3b基因型流行为主[12]。对广州市3a基因型进化树分析发现,本地序列与英国、丹麦等发达国家序列不在同一分支上,却与乌拉圭的序列亲缘性相近;3b基因型进化树显示,广州市3b序列与印度和越南的序列基因型相近。这进一步说明了不同地区间HCV基因型的传播和演化存在复杂的联系,也体现了对本地HCV基因型分布研究的重要性。1b基因型在我国曾长期占据优势地位[4],但近年来在广东地区已被6a基因型取代。本次研究中1b基因型占比虽低于6 a和3a基因型,但其在广州市已存在和流行较长时间,且呈现较高的分化度。
研究发现,广州市男性IDUs中,6a基因型的流行率显著高于其他基因型,而女性IDUs中基因型分布差异无统计学意义。这一结果与既往研究中女性IDUs主要流行1b基因型的结论有所不同[13],可能是由于本次研究中女性样本量较少所致。尽管如此,本研究仍提示性别因素可能影响HCV基因型的分布,未来研究应扩大女性IDUs的样本量,进一步验证该结果。
本研究中,>50岁的IDUs占89.89%,显示中老年群体是HCV感染的高危人群。全国医院感染监控网的监测结果也显示,50~60岁年龄组的HCV阳性率最高,>40岁人群的感染率显著高于≤40岁人群[14]。中老年IDUs的高感染率可能与多种因素有关,包括长期注射毒品、婚外性行为以及多性伴等[15–16]。近年来,中老年人群的高危性行为普遍且多样,性传播风险较高,但相关知识知晓率较低[17–18]。因此,在防控HCV传播时,除了关注血液传播途径外,还应加强对中老年人群性传播的干预措施。
广州市1b基因型占比20.83%,低于6a和3a基因型。尽管如此,1b基因型的耐药性分析显示,所有1b基因型序列均检测出C316N耐药突变,突变率为100%。亚洲地区C316N位点突变率较全球高[19],我国该位点突变率高于亚洲平均水平,达94.2%~100%[20–22]。C316N突变可能导致NS5B RNA依赖性聚合酶的结构变化,进而影响索磷布韦等直接抗病毒药物(DAAs)的疗效[23]。因此,在对广州市IDUs进行DAAs治疗时,应特别关注1b基因型的耐药性,以提高治疗方案的有效性。
本研究样本量有限,尤其是女性IDUs的样本量较少,可能影响结果的代表性。此外,本研究仅对NS5B区进行了基因分型和耐药性分析,未来研究可考虑对HCV全基因组进行测序,以获取更全面的基因型信息和耐药突变情况。
综上所述,广州市IDUs中HCV感染以6a基因型为主,各基因型的输入来源复杂。中老年IDUs是HCV感染的高危人群,需加强防控措施。1b基因型的C316N耐药突变率高达100%,提示在DAAs治疗中应加强对1b基因型耐药性的关注。未来研究应扩大样本量,尤其是女性IDUs的样本量,以进一步验证本研究的结果,并为HCV的防控和治疗提供更全面的参考依据。

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2025年第41卷第9期
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doi: 10.11847/zgggws1147094
  • 接收时间:2025-02-13
  • 首发时间:2026-10-25
  • 出版时间:2025-09-10
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  • 收稿日期:2025-02-13
  • 修回日期:2025-02-24
  • 录用日期:2025-08-13
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    广州市疾病预防控制中心艾滋病预防控制部,广州 510440

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韩志刚,E-mail:
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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