[Clinical observation of continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B]

Zhonghua Gan Zang Bing Za Zhi. 2018 Sep 20;26(9):646-649. doi: 10.3760/cma.j.issn.1007-3418.2018.09.002.
[Article in Chinese]

Abstract

Objective: To observe continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B. Methods: Data of patients with active stage of chronic hepatitis B over the past 6 years were collected and analyzed retrospectively. The incidence of drug resistance mutation and related factors between patients taking LAM or ETV continuously and intermittently were compared with those taking LAM or ETV. Data comparison was performed using χ(2) test. Results: Patients with HBV DNA≥10(5) copies / ml at the time of initial treatment had higher resistance mutation rates than those with HBV DNA < 10(5) copies / ml at either continuous or intermittent treatment, and patients with intermittent treatment had higher resistance mutation rates than those with continuous treatment. Simultaneously, the incidence of drug resistance mutation in LAM and ETV in the first, second and third years were significantly higher in intermittent treatment than that of continuous treatment (P < 0.05). There was a positive correlation between the frequency of drug withdrawal and the rate of drug resistance mutation. There were no individual difference and drug difference between LAM and ETV. Conclusion: In the treatment of chronic hepatitis B with oral nucleoside analogues, drug resistance may occur in either continuous or intermittent treatment. When comparing continuous with intermittent treatment, it suggests that intermittent is more likely to cause viral resistance mutation.

目的: 观察慢性乙型肝炎患者服用拉米夫定(LAM )或恩替卡韦(ETV)抗病毒治疗过程中,持续服药与间断服药(抗病毒治疗12周后,肝脏生物化学指标及HBV DNA转阴,患者自动停药,12周或24周后因HBV DNA > 10(4)拷贝/ml,排除耐药后再服原药治疗)出现病毒耐药变异概率的情况。 方法: 收集近6年的慢性乙型肝炎患者资料,回顾性分析在治疗过程中患者单药持续服用LAM或ETV与间断服用LAM或ETV发生病毒耐药变异的概率及相关因素的差异,计数资料比较采用χ(2)检验。 结果: 初治时HBV DNA≥10(5)拷贝/ml的患者,无论是持续服药或间断治疗,病毒耐药变异比例均大于HBV DNA < 10(5)拷贝/ml的患者;持续与间断治疗的患者比较,间断治疗患者的病毒耐药变异率高于持续治疗的患者。同时,间断治疗的患者,第1年、第2年LAM的病毒耐药变异率以及第1、2、3年ETV的病毒耐药变异发生率远远高于持续治疗的患者(P < 0.05)。间断治疗患者的停药次数与病毒耐药变异发生比呈正相关。LAM及ETV在患者中的应用无个体差异及药品差异性。 结论: 核苷类似物治疗慢性乙型肝炎过程中,无论是持续或间断口服核苷类似物进行抗病毒治疗均有可能发生耐药。两者相比,间断性用药更易导致病毒耐药变异发生。.

Keywords: Entecavir; Hepatitis B, chronic; Lamivudine.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • DNA, Viral / drug effects*
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / administration & dosage*
  • Mutation
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • entecavir
  • Guanine