Rodriguez-Frias Francisco, Jardi Rosendo, Schaper Melanie, Gimferrer Montserrat, Elefsiniotis Ioannis, Tabernero David, Esteban Rafael, Buti Maria
Department of Biochemistry, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
J Med Virol. 2007 Nov;79(11):1671-3. doi: 10.1002/jmv.20982.
Development of hepatitis B virus (HBV)-resistant strains following nucleos(t)ide analog treatment is a major medical concern. This report describes a case of an adult patient with chronic HBV infection, sequentially treated with the nucleos(t)ide analogues, lamivudine, adefovir, and entecavir. During monotherapy with lamivudine, the patient developed lamivudine-resistant variants, which were undetectable during adefovir dipivoxil monotherapy. Twenty-two months after discontinuing lamivudine therapy, the resistant variants were again detected while the patient was receiving entecavir monotherapy. Genotypic analysis by sequencing the HBV polymerase was confirmed with the INNO-LiPA method. The results of this study suggest that entecavir treatment reselected residual lamivudine-resistant HBV variants, possibly because lamivudine-resistant HBV is less susceptible to entecavir than the wild-type virus. Despite the presence of these variants, the patient has had a complete virological response.
核苷（酸）类似物治疗后出现乙型肝炎病毒（HBV）耐药株是一个主要的医学问题。本报告描述了一例慢性HBV感染成年患者的病例，该患者先后接受了核苷（酸）类似物拉米夫定、阿德福韦和恩替卡韦治疗。在拉米夫定单药治疗期间，患者出现了拉米夫定耐药变异株，在阿德福韦酯单药治疗期间未检测到这些变异株。停用拉米夫定治疗22个月后，在患者接受恩替卡韦单药治疗时再次检测到耐药变异株。通过对HBV聚合酶进行测序的基因分型分析经INNO-LiPA方法得以证实。本研究结果表明，恩替卡韦治疗重新选择出了残留的拉米夫定耐药HBV变异株，可能是因为拉米夫定耐药HBV对恩替卡韦的敏感性低于野生型病毒。尽管存在这些变异株，该患者仍获得了完全病毒学应答。
