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High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.
Journal of Clinical and Translational Hepatology ( IF 3.6 ) Pub Date : 2023-06-07 , DOI: 10.14218/jcth.2022.00135s
Alexis Jose-Abrego 1, 2 , Sonia Roman 1, 2 , João Renato Rebello Pinho 3, 4 , Michele Soares Gomes-Gouvêa 3 , Arturo Panduro 1, 2
Affiliation  

Background and Aims Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations. Methods This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool. Results Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18). Conclusions The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

中文翻译:

HBV 基因型 A2 和 H 中出现高频率的抗病毒耐药突变:墨西哥的多药耐药菌株。

背景和目标 拉米夫定 (3TC)、替比夫定 (LdT)、恩替卡韦 (ETV)、阿德福韦 (ADF) 和替诺福韦 (TFV) 是用于治疗乙型肝炎病毒 (HBV) 感染的药物,但特定突变使某些病毒产生耐药性抗病毒药物或获得免疫逃逸能力。这些突变在墨西哥尚未得到彻底调查。本研究旨在估计乙型肝炎病毒抗病毒耐药性和逃逸突变的患病率。方法 这项横断面研究分析了 158 个样本。分别使用旋转柱法、PCR 测定法和桑格测序法对血清样品中的 HBV DNA 进行提取、扩增和测序。使用 Geno2pheno 工具确定 HBV 基因型并测试 HBV 突变。结果 总体而言,68.4%(108/158)的HBV患者感染基因型H,其次是G(11.4%,18/158)、A2(10.8%,17/158)、F1b(6.9.0%,11/ 158)、D (1.9%, 3/158)、E (0.6%, 1/158) 和 5.1% (8/158) 有重组证据。耐药突变的发生率为8.2%(13/158),最常见的组合突变是rt180M+rt204V。值得注意的是,我们发现 rt180M+rt204V+rt173L (n=2) 和 rt180M+rt204V+rt202G (n=1) 组合赋予 3TC、LdT 和 ETV 多药耐药性。A2基因型(11.8%,2/17)、H基因型(10.2%,11/108)发现耐药突变,A2基因型(11.8%,2/17)、H基因型(10.2%,11/108)发现逃逸突变。 11/108)、F1b (9.1%, 1/11) 和 G (5.6%, 1/18)。结论 HBV A2 和 H 基因型抗病毒耐药突变或逃逸突变发生率最高,最早发现 HBV 多重耐药病例在墨西哥。
更新日期:2023-06-07
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