作者
Eun-Sook Park, Ah Ram Lee, Doo Hyun Kim, Jeong-Hoon Lee, Jeong-Ju Yoo, Sung Hyun Ahn, Heewoo Sim, Soree Park, Hong Seok Kang, Juhee Won, Yea Na Ha, Gu-Choul Shin, So Young Kwon, Yong Kwang Park, Byeong-Sun Choi, Yun Bin Lee, Nakcheol Jeong, Yohan An, Young Seok Ju, Su Jong Yu, Hee Bok Chae, Kyung-Sang Yu, Yoon Jun Kim, Jung-Hwan Yoon, Fabien Zoulim, Kyun-Hwan Kim
发表日期
2019/6/1
期刊
Journal of Hepatology
卷号
70
期号
6
页码范围
1093-1102
出版商
Elsevier
简介
Background & Aims
Tenofovir disoproxil fumarate (TDF) is one the most potent nucleot(s)ide analogues for treating chronic hepatitis B virus (HBV) infection. Phenotypic resistance caused by genotypic resistance to TDF has not been reported. This study aimed to characterize HBV mutations that confer tenofovir resistance.
Methods
Two patients with viral breakthrough during treatment with TDF-containing regimens were prospectively enrolled. The gene encoding HBV reverse transcriptase was sequenced. Eleven HBV clones harboring a series of mutations in the reverse transcriptase gene were constructed by site-directed mutagenesis. Drug susceptibility of each clone was determined by Southern blot analysis and real-time PCR. The relative frequency of mutants was evaluated by ultra-deep sequencing and clonal analysis.
Results
Five mutations (rtS106C [C], rtH126Y [Y], rtD134E [E], rtM204I/V, and rtL269I [I …
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ES Park, AR Lee, DH Kim, JH Lee, JJ Yoo, SH Ahn… - Journal of Hepatology, 2019