| TITLE: Genotypic and phenotypic characteristics of HBV entecavir resistance in Chinese patients |
| AUTHORS (FIRST NAME, LAST NAME): Yan Liu1, Zhihui Xu1, Liming Liu1, Xiaodong Li1, Jiuzeng Dai1, Zengtao Yao1, Li Chen1, Siyu Bai1, Shaojie Xin1, Dongping Xu1 |
| Institutional Author(s): |
INSTITUTIONS (ALL): 1. Institute of Infectious Diseases and Liver Failure Research Center, Beijing 302 Hospital, Beijing, China.
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ABSTRACT BODY: Background/Aim: The study aimed to investigate HBV ETV resistance profile of Chinese patients in clinical practice. Methods: Serum samples from 18,419 patients collected from July 2007 to June 2012 in Beijing 302 Hospital were screened. Genotypic resistance was detected by direct PCR sequencing and confirmed by clonal sequencing if necessary. Phenotypic resistance was analyzed by measuring HBV replication capacity under drug pressure in HepG2 cells. Results: ETV-resistant mutations were detected from 646 samples and the incidence had been increased in the past five years (1.91%, 2.23%, 3.54%, 3.96%, and 4.77%). Mutational pattern analysis showed that concomitant with rtM204V/rtM204I, mutations at rt184, rt202, rt250, and two of rt184/rt202/rt250 sites were 57.4%, 22.4% and 14.1%, and 6.1%, respectively (Figure 1). Nineteen percent (123/646) of ETV-resistant samples harbored rtM204I±L80I/L180M-based pattern rather than rtL180M+M204V-based pattern. Among them 70 samples only harbored two resistant mutations (rtM204I+T184I x 39, rtM204I+M250L x 26, rtM204I+M250I x 5). All ETV-resistant strains exhibited varied lower natural replication capacity compared to wild-type strains in vitro. ETV susceptibility of rtL180M+M204V-based ETV-resistant mutants was usually lower than rtM204I-based ETV-resistant mutants. Replication of all tested ETV-resistant strains could be effectively suppressed by tenofovir and adefovir in vitro. In clinical practice, adding-on adefovir was more efficacious than switching-to adefovir as a rescue therapy for ETV-resistant patients. Conclusions: The occurrence of ETV-resistant HBV infection kept growing in the past five years in Chinese patients. ETV-resistant mutational pattern diversified and rtM204I-containing ETV-resistant strains occupied near 1/5 of the patients. ETV-resistant strains could be suppressed by tenofovir or adefovir in vitro; and currently, adding-on adefovir was a practical rescue therapy in clinical practice in China.
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 Figure 1. Incidence of entecavir-resistant mutations in recent five years
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Co-Author Disclosure Status |
| The following authors have completed their AASLD 2013 disclosure: Yan Liu: Disclosure completed | Zhihui Xu: Disclosure completed | Liming Liu: Disclosure completed | Xiaodong Li: Disclosure completed | Jiuzeng Dai: Disclosure completed | Zengtao Yao: Disclosure completed | Li Chen: Disclosure completed | Siyu Bai: Disclosure completed | Shaojie Xin: Disclosure completed | Dongping Xu: Disclosure completed |
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