...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of gastroenterology and hepatology >Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors.
【24h】

Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors.

机译：慢性乙型肝炎患者对拉米夫定的耐药性：临床和病毒学因素的作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Lamivudine resistance is associated with long-term monotherapy for chronic hepatitis B and can lead to potentially serious clinical consequences. Scant information exists regarding the influence of hepatitis B virus variants in the development of resistance. The present study was designed to identify factors predictive of lamivudine resistance, with a particular focus on the role of precore and basal core promoter variants in the setting of hepatitis B e antigen-negative disease. METHODS: Eighty-five patients, representing four major genotypes, were followed prospectively on lamivudine therapy. Resistance was defined as an increase in viral load, with polymerase gene sequencing confirming a lamivudine resistance mutation. Median follow up was 19 months (6-54 months). The Cox proportional hazards model was used to determine variables independently predicting for the early onset of lamivudine resistance. RESULTS: The rate of lamivudine resistance was 6%, 31% and 51% at 12, 24 and 48 months, respectively. Multivariate analysis identified the precore variant, high baseline alanine aminotransferase (ALT), and persistent viremia (at 6 months) as independent predictors of the early development of lamivudine resistance, with rate ratios of 4.93 (95% confidence interval [CI]: 1.32-18.5), 1.22 (95%CI: 1.08-1.49), and 4.73 (95%CI: 1.49-15.0), respectively (P < 0.05). Female sex predicted early resistance (rate ratio 5.27 [95%CI: 1.23-22.5, P < 0.05]) although numbers were small (n = 12). Genotype did not influence treatment response nor time to onset of resistance. CONCLUSION: Patients with precore variant hepatitis B virus are likely to develop lamivudine resistance early and should be considered for alternate first-line monotherapy. In the future, combination antiviral therapy may limit the development of resistance.
机译：背景：拉米夫定耐药性与长期治疗慢性乙型肝炎有关，可能导致严重的临床后果。关于乙型肝炎病毒变体在抗药性发展中的影响的信息很少。本研究旨在确定可预测拉米夫定耐药性的因素，特别关注前核心和基础核心启动子变异在乙型肝炎e抗原阴性疾病中的作用。方法：前瞻性接受拉米夫定治疗的85例患者（代表四种主要基因型）。耐药性被定义为病毒载量的增加，聚合酶基因测序证实了拉米夫定耐药性突变。中位随访时间为19个月（6-54个月）。使用Cox比例风险模型确定独立预测拉米夫定耐药性早期发作的变量。结果：在12、24和48个月时拉米夫定的耐药率分别为6％，31％和51％。多变量分析确定前核心变异，高基线丙氨酸氨基转移酶（ALT）和持续病毒血症（6个月时）是拉米夫定耐药早期发展的独立预测因子，比率为4.93（95％置信区间[CI]：1.32-分别为18.5），1.22（95％CI：1.08-1.49）和4.73（95％CI：1.49-15.0）（P <0.05）。尽管人数很少（n = 12），但女性仍能预测早期抵抗（比率为5.27 [95％CI：1.23-22.5，P <0.05]）。基因型既不影响治疗反应，也不影响耐药发生的时间。结论：具有前核心变异型乙型肝炎病毒的患者很可能会早期产生拉米夫定耐药性，应考虑进行替代的一线单药治疗。将来，联合抗病毒治疗可能会限制耐药性的发展。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号