乙型肝炎病毒前C区1896、基本C区启动子区1762/1764变异对拉米夫定抗病毒疗效的影响及其临床意义

The effects of mutations in pre-core1896 and basic core promoter1762/1764 of Hepatitis B virus on lamivudine therapy and their significance

目的研究乙型肝炎病毒(HBV)前C区G1896A变异和基本C区启动子(BCP)区A1762T/G1764A双变异对拉米夫定(LAM)抗病毒疗效的影响及其临床意义。方法收集上海及其周边地区34例慢性乙型肝炎患者,单用LAM或LAM+聚乙二醇干扰素α-2a进行抗病毒治疗共48周,应用Trugene HBV genotyping试剂盒测定分析治疗前(0周)、治疗过程中(24周)、治疗结束时(48周)及随访结束时(72周)RT区YMDD变异;采用HBV基因多态性检测芯片试剂盒测定前C区1896、BCP区1762/1764位点的变异情况。结果在治疗前有9例患者检测出前C区G1896A变异,均为HBVe抗原(HBeAg)阴性慢性乙型肝炎患者;9例前C区G1896A变异患者中7例治疗应答(77.8%,7/9),BCP区A1762T/G1764A变异在治疗应答者与无应答者中差异无统计学意义;3例患者分别在治疗24和48周时检测到YMDD变异,对治疗均无应答。结论慢性乙型肝炎患者治疗前血清HBV DNA变异状态可能影响LAM抗病毒治疗应答及YMDD耐药变异株的复制能力。

Objective To study the effects of Hepatitis B virus （HBV） pre-eore G1896A and basic core promoter （BCP） A1762T/G1764A mutations on lamivudine （LAM） antiviral therapy and their significance. Methods Serum samples of 34 chronic hepatitis B patients received LAM or polyethylene glycol interferon ot-2a therapy for 48 weeks were collected from Shanghai and its peripheral regions. HBV YMDD mutations on RT domain were determined by Trugene HBV genotyping kit,and the pre-eore 1896 and BCP 1762/1764 mutations were determined by hepatitis B chip before treatment （0 week） , during treatment （ 24 weeks ） , in the end of treatment （ 48 weeks ） and follow up （ 72 weeks ）. Results The pre-eore G1896A mutations were detected at week 0 in 9 patients with HBV e antigen（HBeAg） negative, of whom 77.8% （7/9） had sustained virological response. There were no significant differences between patients with sustained virological response and non-response in terms of the mutations in BCP A1762T/G1764A;YMDD mutant was detected in 3 patients after 24 and 48 weeks treatment. The 3 patients were non-reponse on treatments. Conclusions The status of HBV DNA mutation before antiviral therapy may affeet the outcome of LAM therapy and the replication efficacy of LAM-resistant strains.