上海市公共卫生临床中心2015—2019年乙型肝炎病毒基因突变分析

肝脏 ›› 2020, Vol. 25 ›› Issue (10): 1043-1047.

上海市公共卫生临床中心2015—2019年乙型肝炎病毒基因突变分析

张莉, 孟现民, 董平

201508 上海市公共卫生临床中心药学部(张莉,孟现民,董平); 复旦大学附属华山医院药剂科(张莉)

收稿日期:2020-07-07 出版日期:2020-10-31 发布日期:2020-12-18
通讯作者: 董平,Email:dongping@shphc.org.cn
基金资助:
上海市卫生和计划生育委员会科研课题(201640259)

An analysis of genetic mutations of HBV in a tertiary hospital specialized in infectious disease in Shanghai from 2015 to 2019

ZHANG Li^1,2, MENG Xian-Min¹, DONG Ping¹

1. Department of Pharmacy, Shanghai Public Health Clinical Center, Shanghai 201508, China;
2. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200030, China

Received:2020-07-07 Online:2020-10-31 Published:2020-12-18
Contact: DONG Ping,Email:dongping@shphc.org.cn

摘要/Abstract

摘要： 目的了解上海市慢性乙型肝炎患者的HBV耐药突变情况,分析耐药突变的影响因素。方法选取2015—2019年在上海市公共卫生临床中心进行HBV基因检测的慢性乙型肝炎(chronic hepatitis B,CHB)患者,对其HBV RT区的I169、V173、L180、A181、T184、A194、S202、M204、N236、M250共10个位点的基因突变情况进行统计分析,并统计同期内核苷(酸)类药物(NAs)的消耗,简要分析NAs使用与HBV基因突变的关系;通过比较2019年HBV基因突变组与非突变组的差异,分析性别、年龄、HBV DNA、谷丙转氨酶(ALT)、谷草转氨酶(AST)、HBV血清标志物检测结果以及HBV基因型对基因突变的影响。结果 2015—2019年期间有4 182例进行了HBV基因检测,其中651例发生基因突变,总突变率15.57%,突变率逐年降低;高耐药屏障NAs使用占比逐年提高。上海市HBV突变共有32种模式,M204I、M204V+L180M、M204I+L180M为主要突变模式,分别占总突变例数的32.41%、29.33%、16.44%;拉米夫定耐药率15.06%最高,其次为阿德福韦2.13%和恩替卡韦0.22%,未发现替诺福韦耐药。对影响HBV突变的单因素分析,发现年龄、基因型、ALT、AST、HBeAg、HBeAb与突变有关,进一步进行多因素分析,发现年龄增长和HBeAb阴性为HBV耐药的危险因素。结论 1.2015年-2019年上海市HBV基因突变率逐年降低,可能与高耐药屏障NAs使用增加有关;2.HBV突变模式多样,但以M204I、M204V+L180M、M204I+L180M为主;3. HBV对拉米夫定耐药率高;需高度关注未来HBV对恩替卡韦耐药情况;4.年龄较大和HBeAb阴性的CHB患者更加容易发生HBV基因突变,对NAs耐药。

关键词: 慢性乙型肝炎, 乙型肝炎病毒, 基因突变, 耐药

Abstract: Objective To evaluate mutations of HBV genes and explore the factors affecting mutations in Shanghai. Methods Detection data of gene mutations in HBV reverse transcriptase region (including sites at I169, V173, L180, A181, T184, A194, S202, M204, N236 and M250) of patients with chronic hepatitis B(CHB) in Shanghai Public Health clinical Center from 2015 to 2019 were collected, as well the consumptions of nucleoside (acid) medications (NAs) ; explore the factors influencing mutation out of gender, age, HBV DNA, glutamic oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), HBV sreological markers(HBVM) and genotype by univariate and multivariate analysis. Results 651 out of 4182 samples were detected mutations in HBV from 2015 to 2019, with a mutation rate of 15.57%; the mutation rate decreased along with the increasing consumptions of NAs with a higher genetic barrier year by year. Within 32 genetic mutation patterns of HBV in Shanghai, rtM204I, rtM204V+rtL180M and rtM204I+rtL180M were the dominant patterns with propotion of 32.41%, 29.33% and 16.44%, respectively; the rate of HBV resistant to lamivudine was the highest, followed by adefovir 2.13% and entecavir 0.22%, while no HBV resistant to tenofovir was found. Univariate analysis showed that age, genotype, ALT, AST, HBeAg and HBeAb were related to mutations, while multivariate analysis showed that age growth and HBeAb negative were risk factors of mutations. Conclusion 1. The genetic mutation rate of HBV decreased year by year from 2015 to 2019 in Shanghai, which may relate to the increasing consumptions of NAs with higher resistant barrier;2. HBV genetic mutation patterns are diversified with the dominant patterns of rtM204I, rtM204V+rtL180M and rtM204I+rtL180M; 3. The resistance rate of HBV to lamivudine is the highest; we should pay close attention to HBV resistant to entecavir in the future; 4. CHB patients who are older and HBeAb negative are more prone to mutate in HBV gene and resist to NAs.

Key words: Chroic hepatitis B, Hepatitis B virus, Genetic mutation, Resistance

张莉, 孟现民, 董平. 上海市公共卫生临床中心2015—2019年乙型肝炎病毒基因突变分析[J]. 肝脏, 2020, 25(10): 1043-1047.

ZHANG Li, MENG Xian-Min, DONG Ping. An analysis of genetic mutations of HBV in a tertiary hospital specialized in infectious disease in Shanghai from 2015 to 2019[J]. Chinese Hepatolgy, 2020, 25(10): 1043-1047.

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