Departments of aHepatology bVirology, Croix-Rousse Hospital, Hospices Civils de Lyon cINSERM U1052 dLyon 1 University eInstitut Universitaire de France, Paris, France.
Eur J Gastroenterol Hepatol. 2014 Feb;26(2):146-54. doi: 10.1097/MEG.0b013e328365c3e5.
Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analog (NA)-naive chronic hepatitis B patients with a very low rate of resistance (≤1.2%) over 5 years. The aim of this study was to assess the efficacy of ETV treatment in routine clinical practice and to investigate whether persistence of residual viral replication was the result of the emergence and selection of drug-resistant mutants.
Chronic hepatitis B patients treated with ETV were consecutively recruited from the Department of Hepatology, Hospices Civils de Lyon, France, and were monitored regularly within their routine clinical follow-up. Virological, biochemical, clinical, and tolerance findings were assessed prospectively.
A total of 79 patients were studied, of whom 58% received ETV as a first-line therapy. During ETV therapy (median follow-up 42 months), hepatitis B virus (HBV) DNA became undetectable in 95% of patients. Time to HBV DNA undetectability was significantly shorter in patients with an HBV DNA level less than 4 log10 IU/ml at baseline and in HBeAg-negative patients. Moreover, time to undetectability was significantly shorter in patients with no or only one lamivudine-resistance (LAMr) mutation than in patients with two or more LAMr mutations (P=0.050). No patient had renal-function impairment during ETV therapy.
In routine clinical practice, ETV is effective in both NA-naive and NA-experienced patients, except in patients with HBV strains harboring at least two LAMr mutations. The analysis of viral genome sequence at the time of treatment adaptation could prove useful to personalize antiviral therapy in patients failing a previous line of treatment.
恩替卡韦（ETV）是一种强效的核苷酸类似物（NA）初治慢性乙型肝炎患者病毒复制抑制剂，其耐药率（≤1.2%）在 5 年内非常低。本研究旨在评估 ETV 在常规临床实践中的疗效，并探讨残留病毒复制是否是耐药突变体出现和选择的结果。
法国里昂民事收容所肝病科连续招募了接受 ETV 治疗的慢性乙型肝炎患者，并在常规临床随访中定期对其进行监测。前瞻性评估病毒学、生化、临床和耐受性发现。
共研究了 79 例患者，其中 58%的患者将 ETV 作为一线治疗药物。在 ETV 治疗期间（中位随访时间为 42 个月），95%的患者乙型肝炎病毒（HBV）DNA 检测不到。基线 HBV DNA 水平<4log10 IU/ml 和 HBeAg 阴性的患者达到 HBV DNA 检测不到的时间明显更短。此外，无或仅有一个拉米夫定耐药（LAMr）突变的患者达到检测不到的时间明显短于有两个或更多 LAMr 突变的患者（P=0.050）。在 ETV 治疗期间，没有患者出现肾功能损害。
在常规临床实践中，ETV 对 NA 初治和 NA 经治患者均有效，但对至少有两个 LAMr 突变的 HBV 株患者无效。在治疗适应时对病毒基因组序列进行分析可能有助于为先前治疗失败的患者个体化抗病毒治疗。
