Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Glob Antimicrob Resist. 2017 Mar;8:74-81. doi: 10.1016/j.jgar.2016.10.012. Epub 2016 Dec 23.
To study the prevalence of drug-resistant HBV in patients with therapy failure in a Chinese tertiary referral liver centre.
1223 HBV-infected patients who underwent genotypic resistance testing between 2010-2014 were studied.
3TC genotypic resistance was the most common (46.5%), followed by LdT resistant (46.2%), ETV intermediate (37.9%), ADV resistant (11.4%), TDF intermediate (11.4%) and ETV resistant (1.7%). The 3TC resistance rate increased from 39.8% in 2010 to 56.6% in 2013, before decreasing to 49.5% in 2014, evidence of a lagging effect of l-nucleoside consumption. M204I, N236T and L180M+M204V+V173L/S202G were the most common substitutions for l-nucleoside (3TC and LdT), ADV and ETV genotypic resistant phenotypes, respectively. 3TC-exposed patients showed a high multiple genetic resistance rate (3TC-resistant+LdT-resistant+ETV intermediate; 58.8%). Resistance rates to 3TC, LdT and ETV in HCC patients were significantly higher than in cirrhosis and CHB patients. Resistance rates to different drugs showed no statistical difference between genotype B and C patients, whilst some amino acid substitution showed genotype bias, e.g. N236T incidence in genotype B was significantly higher than in genotype C (43.2% vs. 5.9%; P<0.0001), and genotype C isolates had a significantly higher A181V/T incidence than genotype B (54.9% vs. 19.3%; P<0.0001).
3TC genotypic resistance was most common in this centre, whilst ETV had the lowest resistance rate. HBV genotypes had no impact on antiviral drug resistance, except for some drug resistance substitutions bias. Optional initial therapy and subsequent rescue treatment should be based on knowledge of nucleos(t)ide analogue resistance.
研究中国一家三级转诊肝脏中心治疗失败的患者中乙型肝炎病毒（HBV）耐药的流行情况。
对 2010-2014 年间进行基因耐药性检测的 1223 例 HBV 感染患者进行了研究。
最常见的是拉米夫定（3TC）基因型耐药（46.5%），其次是替比夫定耐药（46.2%）、恩替卡韦中间耐药（37.9%）、阿德福韦耐药（11.4%）、替诺福韦中间耐药（11.4%）和恩替卡韦耐药（1.7%）。3TC 耐药率从 2010 年的 39.8%上升到 2013 年的 56.6%，然后在 2014 年下降到 49.5%，表明 l-核苷类药物的消耗存在滞后效应。M204I、N236T 和 L180M+M204V+V173L/S202G 是 l-核苷（3TC 和替比夫定）、阿德福韦和恩替卡韦基因型耐药表型中最常见的取代物。3TC 暴露患者表现出较高的多种基因耐药率（3TC 耐药+替比夫定耐药+恩替卡韦中间耐药；58.8%）。HCC 患者对 3TC、替比夫定和恩替卡韦的耐药率明显高于肝硬化和 CHB 患者。不同药物的耐药率在基因型 B 和 C 患者之间无统计学差异，但某些氨基酸取代存在基因型偏倚，例如基因型 B 中 N236T 的发生率明显高于基因型 C（43.2%比 5.9%；P<0.0001），而基因型 C 分离株 A181V/T 的发生率明显高于基因型 B（54.9%比 19.3%；P<0.0001）。
该中心最常见的是 3TC 基因型耐药，而恩替卡韦的耐药率最低。HBV 基因型对抗病毒药物耐药性没有影响，但某些耐药性取代物存在偏倚。初始治疗方案和后续挽救治疗方案应基于对核苷（酸）类似物耐药性的了解。
