摘要
目的：了解病毒学反弹的 CHB 患者中 HBV 多聚酶基因序列的情况。方法收集出现病毒学反弹的 HBV 感染者141例，患者的血清样本，患者中诊断符合 CHB 者59例，符合肝硬化者68例，符合原发性肝细胞癌患者14例。曾用阿德福韦酯（ADV）治疗患者51例，曾用拉米夫定（LAM）或替比夫定（LdT）治疗患者39例，曾用恩替卡韦（ETV）治疗患者10例，曾用 LAM 或 LdT 序贯 ADV治疗患者41例。利用 PCR 产物直接测序法检测外周血 HBV DNA 多聚酶基因序列。不同治疗组变异发生率的比较采用χ^2检验。结果141例 HBV 感染者中曾用 ADV 治疗组出现耐药变异20例（20／51，39．2％），曾用 LAM 或 LdT 治疗组出现耐药变异28例（28／39，71．8％），应用 ETV 治疗组出现耐药变异3例（3／10），LAM 或 LdT 序贯 ADV 治疗组出现耐药30例（30／41，82．1％）。出现耐药变异频数最多的为 rtM204I／V／S （35．5％），其次为 rtL180M （22．7％）变异，再次为 rtA181T／V 变异（19．1％）。结论 LAM 或 LdT 序贯 ADV 治疗后出现耐药变异发生率最高，ETV 耐药变异率最低。
Objective To investigate the sequence of hepatitis B virus （HBV）polymerase gene in chronic hepatitis B （CHB）patients with virological rebound.Methods A total of 141 serum samples from patients with viral rebound were collected,and the polymerase gene of HBV was sequenced directly using polymerase chain reaction products.Among the recruited patients,59 cases were diagnosed with chronic hepatitis B （CHB）,68 cases of liver cirrhosis and 14 cases of primary hepatocellular carcinoma.Adefovir dipivoxil （ADV）was administered for 51 cases,lamivudine （LAM）or telbivudine （LdT）for 39 cases, entecavir （ETV）for 10 cases and LAM or LdT switching to ADV for 41 cases.Comparison of mutation rates between groups were compared by χ^2 test.Results Among these 141 patients,drug-resistant mutations were detected in 20 （20/51,39.2%）of ADV-treated patients,28 （28/39,71.8%）of LAM-or LdT-treated patients,3 （3/10）of ETV patients and 30 （30/41,82.1%）of LAM/LdT followed by ADV treated patients.The most prevalent mutations was rtM204I/V/S （35.5%）,followed by rtL180M （22.7%）and then rtA181T/V mutation （19.1%）.Conclusions The resistant mutation rate is the highest in LAM or LdT followed by ADV sequential therapy,while the lowest in ETV therapy.This study suggests that physicians should select the antiviral drugs rationally.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2016年第10期593-596,共4页
Chinese Journal of Infectious Diseases
基金
中国肝炎防治基金会天晴肝病研究基金（CFHPC20132140）
关键词
肝炎病毒
乙型
病毒学反弹
耐药变异
Hepatitis B virus
Virologicalrebound
Resistant mutation
