2010 - 2016年治疗失败患者HBV基因组耐药突变的演变

StephenW

Virus Genes. 2017 Nov 8. doi: 10.1007/s11262-017-1518-z. [Epub ahead of print]
Evolution of drug-resistant mutations in HBV genomes in patients with treatment failure during the past seven years (2010-2016).Zhang HY1,2, Liu LG3,2, Ye CY3,2, Chen CH1,2, Hang SX1,2, Zhu Z1,2, Shen HY2, Huang ZY2, Chen WY4, Xue Y5,6.
Author information
1Department of Clinical Laboratory, The Third People's Hospital of Changzhou, Changzhou, Jiangsu, China.2Liver Research Institute of Changzhou, No. 300 Lanling Road, Changzhou, 213000, Jiangsu, China.3Department of Infectious Diseases, The Third People's Hospital of Changzhou, Changzhou, Jiangsu, China.4School of Medicine, Jiangsu University, Zhenjiang, China.5Department of Infectious Diseases, The Third People's Hospital of Changzhou, Changzhou, Jiangsu, China. [email protected].6Liver Research Institute of Changzhou, No. 300 Lanling Road, Changzhou, 213000, Jiangsu, China. [email protected].

AbstractThe objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010-2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.


KEYWORDS: Hepatitis B virus; Long-term analysis; Mutation; Nucleos(t)ide analogues; Resistance

PMID:29119303DOI:10.1007/s11262-017-1518-z

StephenW

病毒基因。 2017年11月8日。doi：10.1007 / s11262-017-1518-z。 [电子版提前打印]
2010 - 2016年治疗失败患者HBV基因组耐药突变的演变。
张HY1,2，刘LG3,2，叶CY3,2，陈CH1,2，杭SX1,2，朱Z1,2，申HY2，黄ZY2，陈WY4，薛Y5,6。
作者信息

1
    常州第三人民医院检验科，江苏常州
2
    江苏省常州市兰陵路300号常州肝研究所，江苏常州213000
3
    常州第三人民医院传染科，江苏常州
4
    江苏大学医学院，中国镇江。
五
    常州第三人民医院传染科，江苏常州[email protected]。
6
    江苏省常州市兰陵路300号常州肝研究所，江苏常州213000 [email protected]。

抽象

本研究的目的是分析过去七年（2010 - 2016年）治疗失败患者中耐药HBV突变株的流行情况。 2010 - 2016年接受HBV-DNA聚合酶基因突变检测的HBV感染者4055人。包括rtL180，rtA181，rtT184，rtS202，rtM204，rtI233，rtN236，rtI169，rtV173和rtM250的核苷酸（t）I类似物（NAs）抗性突变位置被分析。在30.8％（1248/4055）的治疗失败患者中检测到基因型耐药突变。与LAM，ADV，ETV和多药物相关的耐药突变率分别为27.23％（1104/4055），9.67％（392/4055），3.69％（150/4055）和0.79％（32/4055）。在原发性NA耐药突变中，rtM204I（13.44％，545/4055）发生率更高，其次是rtM204V，rtN236T，rtA181T和rtA181V。对于单碱基突变，rtL180M和rtA181V在过去7年中逐渐增加，而rtM204I / V和rtN236T在2015年后下降。耐药突变的发展与ETV的消耗呈正相关（r = 0.964，P = 0.002） ，与LAM（r = 0.679，P = 0.109）和ADV（r = 0.429，P = 0.354）呈弱相关。此外，在HBV基因型C中，单碱基突变rtA181V和多碱基突变（rtL180M + M204I和rtL180M + M204V + M204I）在基因型C中比在基因型B中更常见（1.94％比0.66％，1.84％比0.16％ 1.02％比0.16％）。在过去7年中，HBV RT区的NA相关突变增加，尤其是LAM。 rtL180M和rtA181T / V的频率在过去七年逐渐增加，值得我们重视。
关键词：

乙型肝炎病毒;长期分析;突变;核苷酸（t）ide类似物;抵抗性

结论：
    29119303
DOI：
    10.1007 / s11262-017-1518-Z