恩替卡韦初治慢性乙型肝炎患者HBV基因型变化情况

HBV genotype changes in entecavir-nave chronic hepatitis B patients

目的:观察恩替卡韦(entecavir,ETV)初治慢性乙型肝炎(chronic hepatitis B,CHB)患者体内乙型肝炎病毒(hepatitis B virus,HBV)基因型的变化情况.方法:选取中山大学附属第三医院随访门诊38例留有系列血清的ETV初治CHB患者为研究对象,其中14例留有基线血清,检测ETV初治基线、1、3、6、9、12、24 mo时间点的血清.标本经提取HBV DNA,巢氏PCR扩增HBV逆转录酶(reverse transcriptase,RT)区基因,凝胶电泳鉴定后行基因测序及基因型分型.结果:38例患者,100份血清纳入分析,所测血清标本中,基因型B型80例,C型20例,未发现其他如A、D、E、F、G、H、I、J等基因型.11例(28.9%)患者在ETV抗病毒治疗过程中基因型发生了改变,6例从C型变成B型,5例从B型变成C型.14例留有基线血清的患者中,5例患者基因型发生了改变,2例从B型变为C型,3例从C型变为B型,进化树分析显示这些患者在基线与基因型改变时间点的基因序列的遗传距离也发生改变.结论:ETV初治CHB患者HBV基因型可发生改变,但其原因及意义有待于进一步研究.

AIM： To investigate the hepatitis B virus（HBV） genotype changes in entecavir（ETV）-na？ve chronic hepatitis B（CHB） patients.METHODS： Thirty-eight ETV-na？ve CHB pa-tients treated and followed at our hospital were retrospectively analyzed.Blood serum samples were collected at months 0,1,3,6,9,12,and 24.HBV DNA was retrieved from those samples and subjected to amplification,sequencing,and genotyping.RESULTS： A total of 100 serum samples were collected from 38 CHB patients included in this study.Among all detected serum samples,geno-type B was detected in 80 cases,genotype C was detected in 20 cases,and genotypes A,D,E,F,G,H,I and J were not detected in those samples.HBV genotype was detected to switch among 11 ETV-na？ve patients.Six patients changed from geno-type C to genotype B,and 5 cases switched from genotype B to genotype C.Of 14 patients who had reserved baseline serum,HBV genotype changed in 5 patients,including 2 patients switching from genotype B to genotype C and 3 patients from genotype C to genotype B.Phylogenetic analysis showed that the genetic distance of genetic se-quences changed between baseline and the time point when HBV genotype changed.CONCLUSION： HBV genotype may change in ETV-naive CHB patients,and the mechanisms require further investigation.