桂西地区869例慢性乙型肝炎病毒基因分型与耐药突变分析
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摘要
目的乙型肝炎病毒(HBV)基因型及耐药突变情况与疾病进展和药物疗效密切相关,有效开展其测定具有重要意义。文中旨在检测桂西地区869例HBV的基因型及耐药突变基因,为临床抗HBV治疗提供依据。方法收集2016年1月至2018年3月右江民族医学院附属医院感染性疾病科门诊及住院的来自桂西地区且HBV DNA>1.0×103IU/mL的869例慢性乙型肝炎病毒携带(CHB)患者。采用PCR和反向点杂交法技术检测其HBV基因分型与耐药突变情况。结果共检出7种基因分型,分别为B基因型304例(34.98%),C基因型268例(30.84%),D基因型147例(16.92%)及B+C基因型、B+D基因型、C+D基因型、B+C+D基因型。63例患者发生耐药突变,耐药突变率为7.25%,其中C基因型31例(49.21%),B基因型19例(30.16%);突变模式有rt204I、rt181V、rt236T、rt180M+rt204V+rt204I等14种,其中rt180M+rt204V突变频率最高(17.46%)。B、C基因型的总体突变率(19%、31%)差异有统计学意义(P<0.05)。结论桂西地区CHB患者HBV基因型多样,主要以B、C基因型为主,且耐药突变率较高,突变模式复杂,这一结果为桂西地区临床抗HBV治疗提供了依据。
Objective The genotypes and drug-resistance mutation of hepatitis B virus(HBV) are closely related to the progression of chronic hepatitis B(CHB) and effects of medication.This study was to identify the genotypes and drug-resistance mutation genes of HBV in West Guangxi and provide some laboratory evidence for anti-HBV treatment.Methods We collected serum samples from 869 CHB patients with HBV DNA >1.0×103 IU/mL,all from West Guangxi,between January 2016 and March 2018.We detected the genotypes and drug-resistance mutation genes in the patients by PCR and reverse dot blot(PCR-RDB).Results A total of 7 genotypes were identified in the patients,including genotypes B in304 cases(34.98%),C in 268(30.84%),D in 147(16.92%),B+C in 28(3.22%),B+D in 22(2.53%),C+D in 1(0.12%) and B+C+D in 1(0.12%).Drug-resistance mutation was observed in 63 cases(7.25%),including 31 cases with genotype C(49.21%) and19 with genotype B(30.16%).Fourteen gene mutation patterns were found in all,including rt204 I,rt181 V,rt236 T,rt180 M+rt204 V,and rt180 M+rt204 V+rt204 I,among which,rt180 M+rt204 V exhibited the highest mutation frequency(17.46%).There was a statistically significant difference between the mutation rates of genotypes B and C(19% vs 31%,P<0.05).Conclusion CHB patients in West Guangxi have a wide variety of genotypes of HBV,mainly including genotypes B and C,with a high rate and complicated patterns of drug-resistance mutation,which has provided some reference for anti-HBV treatment in West Guangxi.
Objective The genotypes and drug-resistance mutation of hepatitis B virus(HBV) are closely related to the progression of chronic hepatitis B(CHB) and effects of medication.This study was to identify the genotypes and drug-resistance mutation genes of HBV in West Guangxi and provide some laboratory evidence for anti-HBV treatment.Methods We collected serum samples from 869 CHB patients with HBV DNA >1.0×103 IU/mL,all from West Guangxi,between January 2016 and March 2018.We detected the genotypes and drug-resistance mutation genes in the patients by PCR and reverse dot blot(PCR-RDB).Results A total of 7 genotypes were identified in the patients,including genotypes B in304 cases(34.98%),C in 268(30.84%),D in 147(16.92%),B+C in 28(3.22%),B+D in 22(2.53%),C+D in 1(0.12%) and B+C+D in 1(0.12%).Drug-resistance mutation was observed in 63 cases(7.25%),including 31 cases with genotype C(49.21%) and19 with genotype B(30.16%).Fourteen gene mutation patterns were found in all,including rt204 I,rt181 V,rt236 T,rt180 M+rt204 V,and rt180 M+rt204 V+rt204 I,among which,rt180 M+rt204 V exhibited the highest mutation frequency(17.46%).There was a statistically significant difference between the mutation rates of genotypes B and C(19% vs 31%,P<0.05).Conclusion CHB patients in West Guangxi have a wide variety of genotypes of HBV,mainly including genotypes B and C,with a high rate and complicated patterns of drug-resistance mutation,which has provided some reference for anti-HBV treatment in West Guangxi.
引文
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[11]Guo X,Wu J,Wei F,et al.Trends in Hepatitis B Virus Resistance to Nucleoside/Nucleotide Analogs in North China from 2009to 2016:A Retrospective Study[J].Int J Antimicrob Agents,2018,52(2):201-209.
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[13]Lee SK,Song MJ,Kim SH,et al.Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis[J].World J Gastroenterol,2017,23(13):2396-2403.
[14]Kim DY,Lee HW,Song JE,et al.Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance[J].J Med Virol,2018,90(3):497-502.
[15]Lampe E,Mello FCA,do Espirito-Santo MP,et al.Nationwide overview of the distribution of hepatitis B virus genotypes in Brazil:a 1000-sample multicentre study[J].J Gen Virol,2017,98(6):1389-1398.
[16]Choi YM,Lee SY,Kim BJ.Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression[J].World J Gastroenterol,2018,24(16):1708-1724.
[2]Croagh CM,Desmond PV,Bell SJ.Genotypes and viral variants in chronic hepatitis B:A review of epidemiology and clinical relevance[J].World J Hepatol,2015,7(3):289-303.
[3]王忠琼,刘翼,夏国栋,等.前列地尔对乙肝肝硬化患者血清炎性因子及肝功能的影响[J].医学研究生学报,2017,30(6):611-614.
[4]唐慧娴,王长军,张琪.CRISPR/Cas9技术用于清除乙型肝炎病毒的研究进展[J].医学研究生学报,2017,30(8):865-868.
[5]Boyce CL,Ganova-Raeva L,Archampong TNA,et al.Identification and comparative analysis of hepatitis B virus genotype D/Erecombinants in Africa[J].Virus Genes,2017,53(4):538-547.
[6]Wi J,Jeong MS,Hong HJ.Construction and Characterization of an Anti-Hepatitis B Virus preS1 Humanized Antibody that Binds to the Essential Receptor Binding Site[J].J Microbiol Biotechnol,2017,27(7):1336-1344.
[7]常彩芳,钟海振,韩永平.替诺福韦酯治疗多重耐药慢性乙型肝炎及与HBV基因型关系的研究[J].中国中西医结合消化杂志,2017,12:910-914.
[8]卢玉香,周筠.广东省潮州地区献血者乙肝感染血清学和分子生物学特征[J].分子诊断与治疗杂志,2018,10(1):34-37+55.
[9]文晓飞,马庆庆,熊玮,等.遵义地区慢性乙型病毒性肝炎少数民族患者检测基因分型与耐药变异的相关性和意义[J].临床检验杂志(电子版),2017,6(2):200-201
[10]覃羽华,岑光旅,王俊利,等.桂西地区慢性乙型肝炎基因分型及其临床特点[J].检验医学与临床,2012,9(2):138-140.
[11]Guo X,Wu J,Wei F,et al.Trends in Hepatitis B Virus Resistance to Nucleoside/Nucleotide Analogs in North China from 2009to 2016:A Retrospective Study[J].Int J Antimicrob Agents,2018,52(2):201-209.
[12]European Association For The Study Of The L.EASL clinical practice guidelines:Management of chronic hepatitis B virus infection[J].J Hepatol,2012,57(1):167-185.
[13]Lee SK,Song MJ,Kim SH,et al.Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis[J].World J Gastroenterol,2017,23(13):2396-2403.
[14]Kim DY,Lee HW,Song JE,et al.Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance[J].J Med Virol,2018,90(3):497-502.
[15]Lampe E,Mello FCA,do Espirito-Santo MP,et al.Nationwide overview of the distribution of hepatitis B virus genotypes in Brazil:a 1000-sample multicentre study[J].J Gen Virol,2017,98(6):1389-1398.
[16]Choi YM,Lee SY,Kim BJ.Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression[J].World J Gastroenterol,2018,24(16):1708-1724.
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