唐山地区CHB患者HBV基因型与耐药种类和耐药位点的分析研究

Analysis of HBV genotypes and drug resistance species and drug resistance loci of CHB patients in Tangshan region

目的探讨唐山地区慢性乙型肝炎病毒(CHB)患者乙型肝炎病毒(HBV)基因分型,核苷酸类抗病毒药物的耐药种类分布和耐药位点的相关性。方法选择2009年10月-2014年4月就诊于唐山市传染病医院门诊和住院的467例慢性乙型肝炎病毒患者,通过使用毛细管电泳仪采用双脱氧终止法测序技术,对患者血清进行HBV基因分型和耐药位点的检测,使用统计学软件对数据进行统计分析。结果唐山地区CHB患者的467例样本中检测出HBV基因型445例,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%;共检出耐药患者283例,其中对恩替卡韦、拉米夫定和替比夫定多药耐药的160例占56.54%;对阿德福韦酯的主要耐药位点是rtA181V/T/S突变,其次是rtA181V/T/S和rtN236T同时突变,B基因型与C基因型对阿德福韦酯的耐药位点突变分布比较差异有统计学意义(P<0.05);对拉米夫定、恩替卡韦和替比夫定多药耐药的主要耐药位点是rtL180M和rtM204I/V/S同时突变,其次是单独rtM204I/V/S突变。结论唐山地区HBV感染者的基因型主要以C基因型为优势基因型;通过对耐药位点的分析,B基因型CHB患者应用阿德福韦酯不易耐药,HBV基因型B型和C型的CHB患者对拉米夫定、恩替卡韦和替比夫定耐药的多药耐药位点分布无差异。

OBJECTIVE To investigate the correlation of the HBV genotypes,nucleotide antiviral drug resistant species＇ distribution and drug resistance loci of patients with chronic hepatitis B（CHB）in Tangshan region.METHODS A total of 467 patients with chronic hepatitis B treated in Tangshan Hospital for Infectious Diseases rom Oct.2009 to Apr.2014 were selected.The capillary electrophoresis apparatus with the dideoxy sequencing technology was adopted for serum HBV genotyping and detection of drug resistance loci.Statistical software was used for statistical analysis of data.RESULTS A total of 455 cases of patients with hepatitis B genotype were detected,including 64 cases of genotype B（14.38%）,380 cases of genotype C（85.39%）,and 1 case of genotype D（0.22%）.Totally 283 patients with drug resistance were detected,including 160 cases were multi-resistant to entecavir,lamivudine and telbivudine（56.54%）.The main resistant loci of adefovir dipivoxil was rtA181 V/T/S mutation,followed by rtA181 V/T/S and rtN236 T mutations at the same time,and there was a significant difference in the distribution of resistant mutations of adefovir dipivoxil between genotype B and genotype C（P〈0.05）.The main multidrug-resistant loci of lamivudine,entecavir and telbivudine was rtL180 Mand rtM204 I/V/S mutation at the same time,and the second was rtM204 I/V/S mutation alone.CONCLUSIONGenotype C is the main genotype of HBV infected genotypes in Tangshan region.Through the analysis of drug resistant loci,adefovir dipivoxil is not susceptible to drug resistance in genotype B CHB patients.There was no difference in the distribution of multi drug resistance sites to lamivudine,entecavir and telbivudine between HBV genotype B and genotype C CHB patients.