Chinical and phenotipic analyses of untypical adefovir-resistanence-associated mutation rtN238T of hepatitis B virus
10.3760/cma.j.issn.1003-9279.2015.02.015
- VernacularTitle:乙型肝炎病毒非经典阿德福韦耐药相关突变rtN238T的临床分析与表型鉴定
- Author:
Xiaodong LI
1
;
Yaqun QIN
;
Jingjing WU
;
Fan LI
;
Hao LIAO
;
Rongjuan CHEN
;
Dongping XU
Author Information
1. 解放军医学院
- Keywords:
Hepatitis B virus;
Mutation;
Drug resistance
- From:
Chinese Journal of Experimental and Clinical Virology
2015;29(2):139-141
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify clinical prevalence of untypical adefovir-resistant mutations of hepatitis B virus (HBV),and to analyze their phenotypic characteristics.Methods 1741 patients with chronic HBV infection were evolved.Untypical adefovir-resistant mutations were analyzed by direct sequencing.Longitudinal analysis was performed by clonal sequencing.Wild-type and mutant HBV genomic amplicons were constructed into pTriEx-HBV 1.1 vector and transfected into HepG2 cells.The replication capacity and the 50％ effective concentration of drugs (EC50) were calculated.Results Patients treated with adefovir alone were more likely to develop rtN238T mutation than those treated with other nucleos(t) ide drugs (x2 =17.10,P ＜ 0.01).The patient received adefovir for 47 months,and then viral rebound and biochemical breakthrough occurred with detection of rtN238T + A181V and rtN238T mutation.Switching-to entecavir therapy suppressed HBV DNA and ALT to an undetectable level and converted all viruses into wild type ones.The reulsts of viral replication capacity showed that rtN238T + A181V strain was higher than rtA181V strain (t =9.54,P ＜ 0.01).Compared to the wild type virus,rtN238T + A181V variant was relatively less susceptible to adefovir.Conclusions rtN238T mutation conferred no resistance to ADV but enhanced natural replication capacity,hence it might represent a novel compensatory drug-resistant mutation for adefovir.
