贵州地区269例慢性乙型肝炎患者病毒基因型与耐药分析

A study of the correlationship between HBV genotypes and virus genome drug resistance sites in CHB infection patients 269 cases receiving nucleoside(nucleotide)analogs anti-viral treatment in Guizhou

目的:探讨贵州地区269例经核苷类似物(NAs)治疗的慢性乙型肝炎(CHB)患者乙型肝炎病毒(HBV)耐药特征与基因型的相关性。方法 :对2013年12月至2015年12月来自贵州省各地就诊于贵阳市公共卫生救治中心经NAs治疗48周以上,HBV DNA>2 000 IU/m L的CHB患者269例,采用PCR与反向点杂交法进行外周血HBV基因型及耐药位点检测,分析耐药突变特征与HBV基因型的相关性。结果:269例患者中,B基因型139例,C基因型117例,BC混合感染10例,D基因型3例,在B型和C型患者中,HBV耐药89例,占34.77%,其中拉米夫定、替比夫定、阿德福韦酯、恩替卡韦在变异患者中的比例分别为86.52%、67.42%、20.22%、28.09%,多耐药患者63例。C基因型rtL180M和rtL181V突变明显多于B基因型,差异有统计学意义(P=1.035,P=0.026);男性患者中rtL180M突变明显多于女性,差异有统计学意义(P=0.035);89例耐药患者中B、C基因型间差异无统计学意义(P=0.727)。结论 :CHB患者耐药基因突变形式复杂,主要对拉米夫定和替比夫定耐药,多药耐药患者比例较高,rtM180L、rtM204V、rtM204I 3个位点检出突变率高,检测者中耐药突变在基因型间的分布无明显差异。

Objective To explore the relationship between hepatitis B virus （HBV） genotypes and virus genome drug resistance sites in chronic hepatitis B （CHB） patients receiving nucleoside （nucleotide）analogs （NAs） anti-viral treatment in Guizhou. Methods The studied CHB patients from Guizhou each region received NAs anti-viral treatment in the Guiyang public health treatment center during the period of December of 2013 to December of 2015. We used the combined techniques of nested polymerase chain reaction and reverse dot blot to detect the HBV genotypes and virus genome drug resistance sites in peripheral blood samples. The correlationship between the HBV genotypes and virus genome drug resistance sites was also explored. Results In a total of 269 cases, there were 139 genotype B cases, 117 genotype C cases, 10 genotype B＆C mixed cases and 3 genotype D cases. In the subgroup with genotype B and C infection, there were overall 89 cases with sort of drug resistance sites, among which the resistance to lamivudine were 86.52%, telbivudine were 67.42%, adefovir dipivoxil were 20.22% and entecavir were 28.09% respectively and there were 63 cases with multiple drug resistance; In the cases with genotype C, the frequencies of mutaion rtL180M or mutaion rtL181V were significantly higher than those in the cases with genotype B （P = 1.035, P = 0.026）. Also, the frequency of mutation rtL180M in the male patients was significantly higher than that in the female patients （P = 0.035）. Finally, the distribution of genotype B and genotype C were statistically even among the patients with certain kind of drug resistance sites （P = 0.727）. Conclusions A complex pattern of drug resistance in the virus genome were found and the commonest resistance drugs were LAM and LdT with rtM18OL,rtM204V,rtM204I being the commonest mutation sites. In addition, the oceurance of multiple drug resistance was high and there were no statistical significance of resistance sites among various genotypes.