CHB感染者耐核苷(酸)类似物种类与HBV基因分型的研究
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摘要
目的探讨唐山地区慢性乙型肝炎病毒(CHB)感染者的年龄、性别特征、耐药种类与乙型肝炎病毒(HBV)基因分型之间的相关性。方法选择2009年10月-2014年4月医院慢性乙型肝炎病毒患者467例为研究对象,通过毛细管电泳仪采用双脱氧终止法测序技术对患者的血清进行HBV基因分型的检测,并分析HBV基因分型与耐药种类之间的相关性。结果唐山地区CHB感染者的467份样本中未检出基因型22份,已检测出HBV基因型的445份样本中共检出B、C、D三种基因型,其中B基因型64例占14.38%,C基因型380例占85.39%,D基因型1例占0.22%,C基因型为优势基因型(P<0.001)。已检测出B、C基因型的444例感染者中,<40岁和≥40岁分别占34.68%(154/444)和65.32%(290/444),差异有统计学意义(P<0.001);男性和女性感染者中,均以C基因型为主;男性感染者355例多于女性感染者89例(P<0.001);男性和女性CHB感染者不同基因分型间耐药种类的差异无统计学意义(P=0.345)。结论唐山地区CHB感染者主要耐药种类是拉米夫定、恩替卡韦和替比夫定的同时耐药,其次是阿德福韦酯的耐药。
OBJECTIVE To investigate the relationship between age,gender,drug resistance and HBV genotyping in patients infected with chronic hepatitis B virus(CHB)in Tangshan area.METHODS A total of 467 infectors with chronic hepatitis B virus(CHB)from Oct.2009 to Apr.2014 were selected.HBV genotyping and drug resistance mutation in the serum of infected patients were detected by using capillary electrophoresis and dideoxy termination sequencing technique.Data were collected and the correlation between HBV genotyping and drug resistance was analyzed.RESULTS No genotype was detected in 22 out of the 467 samples of CHB-infected patients in Tangshan area.Three genotypes were detected in the 445 samples detected with HBV genotypes,64 of which belonged to genotype B(14.38%),380 cases were genotype C(85.39%),and 1 case was genotype D(0.22%),with genotype C as the dominant genotype(P<0.001).Among 444 cases of B and C genotypes detected,34.68%(154/444)and 65.32%(290/444)were under 40 years old and over 40 years old,respectively,the difference was(P<0.001).In both male and female patients,genotype C was predominant.There were 356 male patients,significantly more than 89 female patients(P<0.001).There was no significant difference in drug resistance between male and female CHB-infected patients with different genotypes(P=0.345).CONCLUSION The main type of drug resistance of CHB-infected patients in Tangshan is simultaneous resistance to lamivudine,entecavir and telbivudine,followed by resistance to adefovir dipivoxil.
OBJECTIVE To investigate the relationship between age,gender,drug resistance and HBV genotyping in patients infected with chronic hepatitis B virus(CHB)in Tangshan area.METHODS A total of 467 infectors with chronic hepatitis B virus(CHB)from Oct.2009 to Apr.2014 were selected.HBV genotyping and drug resistance mutation in the serum of infected patients were detected by using capillary electrophoresis and dideoxy termination sequencing technique.Data were collected and the correlation between HBV genotyping and drug resistance was analyzed.RESULTS No genotype was detected in 22 out of the 467 samples of CHB-infected patients in Tangshan area.Three genotypes were detected in the 445 samples detected with HBV genotypes,64 of which belonged to genotype B(14.38%),380 cases were genotype C(85.39%),and 1 case was genotype D(0.22%),with genotype C as the dominant genotype(P<0.001).Among 444 cases of B and C genotypes detected,34.68%(154/444)and 65.32%(290/444)were under 40 years old and over 40 years old,respectively,the difference was(P<0.001).In both male and female patients,genotype C was predominant.There were 356 male patients,significantly more than 89 female patients(P<0.001).There was no significant difference in drug resistance between male and female CHB-infected patients with different genotypes(P=0.345).CONCLUSION The main type of drug resistance of CHB-infected patients in Tangshan is simultaneous resistance to lamivudine,entecavir and telbivudine,followed by resistance to adefovir dipivoxil.
引文
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[8]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年版)[J].中国肝脏病杂志(电子版),2015,7(3):1-18.
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[11] Ahn SH,Yuen L,Han KH,et al.Molecular and clinical characteristics of hepatitis B virus in Korea[J].J Med Virol,2010,82(7):1126-1134.
[12] Schulz TR,Edwards R,Thurnheer MC,et al.Hepatitis B among immigrants from Myanmar:genotypes and their clinical relevance[J].J Med Virol.2018,90(2):271-276.
[13] Revill P,Locarnini S.Viral factors and predicting disease outcomes in chronic hepatitis B[J].Gut,2015,64(2):191-193.
[14]李东,张苏晗,杨秀惠,等.福建地区乙型肝炎病毒基因型分布及特征[J].中国热带医学,2017,17(1):27-31.
[15] Zhang Q,Liao Y,Chen J,et al.Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China[J].Sci Rep,2015,5(1):17413.
[16] Sugauchi F,Orito E,Ichida T,et al.Hepatitis B virus of genotype B with or without recombination with genotype C over the precore region plus the core gene[J].J Virol,2002,76(12):5985-5992.
[17] Mokaya J,McNaughton AL,Hadley MJ,et al.A systematic review of hepatitis B virus(HBV)drug and vaccine escape mutations in Africa:a call for urgent action[J].PLoS Negl Trop Dis.2018,12(8):e0006629.
[2] 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.
[3] Chan HL.Significance of hepatitis B virus genotypes and mutations in the development of hepatocellular carcinoma in Asia[J].J Gastroenterol Hepatol,2011,26(1):8-12.
[4] Zhang M,Ge G,Yang Y,et al.Decreased antigenicity profiles of immune-escaped and drug-resistant hepatitis B surface antigen(HBsAg)double mutants[J].Virol J,2013,10(1):292.
[5] Chan HL,Tsang SW,Liew CT,et al.Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection[J].Am J Gastroenterol 2002,97(2):406-412.
[6] Chan HL,Wong ML,Hui AY,et al.Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigen-positive patients[J].J Clin Microbiol,2003,41(3):1277-1279.
[7] Lin CL,Kao JH.The clinical implications of hepatitis B virus genotype:recent advances[J].J Gastroenterol Hepatol,2011,1:123-130.
[8]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年版)[J].中国肝脏病杂志(电子版),2015,7(3):1-18.
[9] Kostaki EG,Karamitros T,Stefanou G,et al.Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach[J].Elife,2018,7:e36709.
[10] 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.
[11] Ahn SH,Yuen L,Han KH,et al.Molecular and clinical characteristics of hepatitis B virus in Korea[J].J Med Virol,2010,82(7):1126-1134.
[12] Schulz TR,Edwards R,Thurnheer MC,et al.Hepatitis B among immigrants from Myanmar:genotypes and their clinical relevance[J].J Med Virol.2018,90(2):271-276.
[13] Revill P,Locarnini S.Viral factors and predicting disease outcomes in chronic hepatitis B[J].Gut,2015,64(2):191-193.
[14]李东,张苏晗,杨秀惠,等.福建地区乙型肝炎病毒基因型分布及特征[J].中国热带医学,2017,17(1):27-31.
[15] Zhang Q,Liao Y,Chen J,et al.Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China[J].Sci Rep,2015,5(1):17413.
[16] Sugauchi F,Orito E,Ichida T,et al.Hepatitis B virus of genotype B with or without recombination with genotype C over the precore region plus the core gene[J].J Virol,2002,76(12):5985-5992.
[17] Mokaya J,McNaughton AL,Hadley MJ,et al.A systematic review of hepatitis B virus(HBV)drug and vaccine escape mutations in Africa:a call for urgent action[J].PLoS Negl Trop Dis.2018,12(8):e0006629.