慢性乙型肝炎患者血清HBV恩替卡韦耐药基因突变模式调查*

doi:10.3969/j.issn.1672-5069.2022.03.009

Abstract

Abstract: Objective The aim of this study was to investigate entecavir resistance gene mutation in nucleosi(t)de-treated patients with chronic hepatitis B (CHB). Methods 107 nucleosi(t)de-treated patients with CHB and entecavir-resistance mutation were enrolled in our hospital between October 2016 and October 2020. Serum gene amplification of HBV RT was conducted by nested PCR, and the genotypes were identified by MEGA4 software. The HepG2 cells were transfected by liposome in vitro with different HBV mutants, the cells were intervened by lamivudine, adefovir, entecavir and tenofovir, and the supernatant HBV DNA loads were detected by PCR. Results Out of the 107 nucleosi(t)de-treated patients with CHB in our series, the percentages of entecavir resistance gene rtS202G/M204V/L180M was 40.2%, significantly higher than in patients with rtT184A/M204V/L180M(22.2%), rtT184L/M204V/L180M(23.4%), rtS202G/M204i/L180M(3.7%), rtM250V/M204V/L180M(5.6%), rtM250L/M204I/L180M(5.6%) and rtT184I/S202G/M204V/L180M(5.6%) infections (P<0.05); 38.3% patients had received lamivudine, significantly higher than 22.4% receiving adefovir therapy in our series(P<0.05); serum HBV DNA loads in 36 patients with rtT184^sub mutant infection was (3.0±0.5)lgIU/ml, and in 10 with rtT184/S202^sub infection was (4.1±0.8) lgIU/ml, both significantly higher than [(1.9±0.2)lgIU/ml, P<0.05] in 47 patients with rtS202^sub infection or [(2.1±0.2)lgIU/ml, P<0.05] in 14 patients with rtM250^sub infection; the supernatant HBV DNA load in entecavir-intervened cells carrying rtS202G/M204V/L180M mutant was (3.1±0.1)lg IU/ml, significantly higher than [(2.1±0.1 lg IU/ml, P<0.05] in cells carrying rtT184A/M204V/L180M mutants, no significant differences in lamivudine- or adefovir-treated cells(P>0.05), and they both decreased to undetectable in tenofovir-intervened cells. Conclusion The superior entecavir-resistance mutation in nucleosi(t)de-treated patients with CHB is rtS202G/M204V/L180M infection, and they are resistant to lamivudine or adefovir, but fortunately, they still sensitive to tenofovir intervention.

Key words: Hepatitis B, Nucleosi(t)de-treatment, Drug resistance gene, Mutant infection, Tenofovir

Wang Guangli, Xu Huan, Dong Dandan, et al. Entecavir resistance gene mutation in nucleosi(t)de-treated patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2022, 25(3): 339-342.

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Entecavir resistance gene mutation in nucleosi(t)de-treated patients with chronic hepatitis B

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