Jardi R, Rodriguez-Frias F, Schaper M, Ruiz G, Elefsiniotis I, Esteban R, Buti M
Department of Biochemistry, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
J Viral Hepat. 2007 Dec;14(12):835-40. doi: 10.1111/j.1365-2893.2007.00877.x.
It has been suggested that lamivudine therapy can preselect for hepatitis B virus (HBV) variants associated with resistance to entecavir (ETV) treatment. The aim of this study was to determine the prevalence of HBV variants associated with ETV resistance (rtI169T, rtT184G, rtS202I, rtM250V) in naive patients before and during lamivudine therapy. This retrospective study includes 111 untreated patients with chronic HBV infection, who were later treated with lamivudine therapy for at least 18 months. Serum samples were obtained before and during treatment. Variants related with ETV drug resistance were analysed by sequencing the HBV reverse transcriptase. Prior to lamivudine treatment, three cases (2.7%) had substitutions in the HBV polymerase gene corresponding to variants associated with ETV resistance (rtS202S/I). None of these patients had lamivudine-resistant variants. During lamivudine treatment, substitutions associated with ETV resistance were detected in 10 (9%) nonresponding patients who had not presented these changes before treatment. In 2/10 cases, these changes were observed before detection of lamivudine-resistant substitutions. In 10 of 12 nonresponders, one of them with ETV-related variants prior to treatment, these variants persisted to the end of therapy. Detection of variants related to ETV drug resistance in untreated patients with chronic HBV infection indicates that these variants are present in a significant proportion of the HBV quasispecies. This fact, as well as the emergence of ETV-resistant variants during lamivudine treatment, should be kept in mind when selecting candidates for ETV therapy.
有人提出，拉米夫定治疗可能会预先选择出与对恩替卡韦（ETV）治疗耐药相关的乙型肝炎病毒（HBV）变异体。本研究的目的是确定初治患者在拉米夫定治疗前及治疗期间与ETV耐药相关的HBV变异体（rtI169T、rtT184G、rtS202I、rtM250V）的流行情况。这项回顾性研究纳入了111例未经治疗的慢性HBV感染患者，这些患者随后接受了至少18个月的拉米夫定治疗。在治疗前及治疗期间采集血清样本。通过对HBV逆转录酶进行测序来分析与ETV耐药相关的变异体。在拉米夫定治疗前，3例患者（2.7%）的HBV聚合酶基因发生了与ETV耐药相关的变异体对应的替换（rtS202S/I）。这些患者均无拉米夫定耐药变异体。在拉米夫定治疗期间，在10例（9%）治疗无应答患者中检测到了与ETV耐药相关的替换，这些患者在治疗前未出现这些变化。在10例中的2例中，这些变化在检测到拉米夫定耐药替换之前就已观察到。在12例无应答者中的10例中，其中1例在治疗前就有与ETV相关的变异体，这些变异体持续到治疗结束。在未经治疗的慢性HBV感染患者中检测到与ETV耐药相关的变异体表明，这些变异体在HBV准种中占相当比例。在选择ETV治疗的候选患者时，应牢记这一事实以及拉米夫定治疗期间出现ETV耐药变异体的情况。
