慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析

实用肝脏病杂志圆园19年1月第22卷第1期J Prac Hepatol，Jan.2019.Vol.22No.1··

·病毒性肝炎·慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析*张欢欢，杨欢，沈思兰，陈佳婕，宣彬彬

【摘要】目的探讨慢性乙型肝炎（CHB）患者HBV基因型及其耐药突变发生情况。方法纳入240例接受核苷（酸）类似物单药或联合或序贯的CHB患者，采用PCR扩增HBV逆转录（RT）区和序列测定鉴定耐药基因

突变，采用HBV S基因测序法鉴定基因型。结果在35例单用拉米夫定的CHB患者中，发生耐药突变14例（40.0%），突变位点为rtL80I/V、rtVl73L、rtLl80M、rtM204V/I和rtV207I，23例单用阿德福韦者发生耐药突变11

三士道例（47.8%），突变位点为rtAl81T/V、rtS213T/N、rtV214A、rtQ215S/H/P、rtl233V、rtN236T、rtP237H和rtN/H238A/K/D/S，70例单用恩替卡韦者发生耐药突变10例（14.3%），突变位点为rtM204I，12例单用替比夫定者发生耐药

突变5例（41.7%），突变位点为rtI169T、rtL180M、rtT184G/S/A/I/L/F、rtS202I/G、rtM204V和rtM250

V/I/L，100例接受

联合或序贯者发生耐药突变51例（51.0%），突变位点为rtA194T，恩替卡韦患者耐药突变发生率最低（P<0.05）；240例CHB患者中，HBV基因B型21例（8.8%）、C型216例（90.0）和D型3例（1.2%）；在发生耐药突

变的91例患者中，B型6例（6.6%）、C型83例（91.2%）和D型2例（2.2%，x2=1.22，P＞0.05）；在发生耐药突变的6

例B型感染者中有2例（33.3%）和83例C型感染者中有15例（18.1%）发生了多重耐药突变。结论检测CHB患

者感染HBV基因型并及时获得耐药突变基因分布，将有助于指导临床。

【关键词】慢性乙型肝炎；核苷（酸）类似物；HBV基因型；耐药突变

上海市交通港口局DOI：10.3969/j.issn.1672-5069.2019.01.012

Distribution of HBV genotypes and drug-resistant mutations in patients with chronic hepatitis Btv搜查线

Zhang Huanhuan，Yang Huan，Shen Silan，et al.Clinical Laboratory，Affiliated Tongren Hospital，Shanghai JiaoTong

University，Shanghai200335，China

【Abstract】Objective To investigate the distribution of HBV genotypes and drug-resistant mutations in

patients with chronic hepatitis B（CHB）.Methods240patients with CHB receiving monotherapy or swift from

one to another of nuleos（t）ide analogues（NAs）for at least three months were recruited in this study，and the

drug resistance mutation was assayed by sequencing reverse transcription area and the HBV genotypes were

detected by sequencing HBV S gene.Results The resistant mutation rate in35patients treated by lamivudine

日内瓦会议

was40.0%with the resistant mutation sites of rtL80I/V，rtVl73L，rtLl80M，rtM204V/I，and rtV207I；the resistant

mutation rate in23patients receiving adefovir was47.8%with the mutation sites of rtAl81T/V，rtS213T/N，rtV214A，rtQ215S/H/P，rtl233V，rtN236T，rtP237H，rtN/H238A/K/D/S；the mutation rate in70receiving entecavir was

14.3%with the mutation sites of rtM204I；the resistant mutation rate in12patients receiving telbivudine41.7%

with the mutation sites of rtI169T，rtL180M，rtT184G/S/A/I/L/F，rtS202I/G，rtM204V and rtM250V/I/L；the resistance

mutation rate in100patients with combination or swift therapy was51.0%with the mutation sites of rtA194T；out

of240patients with CHB，21（8.8%）were with type B，216（90.0%）were with type C，and3（1.2%）were with

tornado

type D hepatitis B viral infection；out of the91patients with drug resistance mutations，6（6.6%）w

ere with type

B，83（91.2%）were with type C，and2（2.2%）were with type D infection；multidrug resistance mutations occurred

in2（33.3%）of6patients with type B and15（18.1%）of83type C infection.Conclusion Surveillance of HBV

genotypes and resistance mutations in patients with CHB receiving NAs therapy might help improve the clinical

response.

【Key words】Hepatitis B；Nuleos（t）ide analogues；HBV genotypes；Drug resistance mutations

*基金项目：上海市长宁区科学技术委员会科研基金资助项目（编号：CNKW2014Z02）

作者单位：200335上海市上海交通大学附属同仁医院检验科（张欢欢，陈佳婕，宣彬彬）；内分泌内科（杨欢）；感染病科（沈思兰）

核雾霾第一作者：张欢欢，女，35岁，大学本科，主管技师。主要从事分子遗传学诊断研究。E-mail:ZHH2504@shtrhospital

通讯作者：杨欢，E-mail:YH1497@shtrhospital

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