乙型肝炎病毒前-C区1896和基本C区启动子区1762、1764 双突变及YMDD变异对拉米呋啶治疗的影响

目的:研究乙型肝炎病毒前-C区G1896A突变和基本C区启动子区A1762T、G1764A双突变对拉米呋啶治疗的影响。 方法:采用直接测序法对服药前、中、后的血清标本的逆转录多聚酶区及前-C、基本C区启动子区进行检测。 结果:①前-C区G1896A和基本C区启动子区A1762T、G1764A双突变在出现治疗中病毒学反弹与未出现治疗中病毒学反弹患者间及发生血清学转移与未发生血清学转换患者间差异无显著性(P>0.05)；②G1896A突变在发生YMDD变异和未发生YMDD变异的患者间差异有显著性(P<0.05)，发生YMDD变异的患者很少伴有G1896A突变率低(9%)；③出现治疗中病毒学反弹的患者YMDD变异增加，与未出现治疗中病毒学反弹的患者比较差异有显著性(P<0.05)。 结论:前-C区G1896A和基本C区启动子区A1762T、G1764A双突变对拉米呋啶治疗后出现的治疗中病毒学反弹和血清学转换没有影响；在G1896A突变株YMDD变异减少；YMDD变异株的出现对治疗后出现的治疗中病毒学反弹有影响；YMDD变异可能是加剧肝细胞损伤引起治疗中病毒学反弹的因素之一。

Mutations in PreC and basic core promoter of hepatitis B virus and effects of YMDD mutants on Lamivudine therapy

Objective To investigate of the mutations in the PreC G1896A and in the basic core promoter (BCP) A1762T and G1764A as well as the effects of YMDD mutants on Lamivudine therapy against chronic hepatitis B virus (HBV) infection.Methods Serum samples were obtained before, during and after therapy. Parts of the HBV polymerase gene flanking the YMDD motif and the PreC/BCP region were sequenced after polymerase chain reaction (PCR) amplification. Results ①There were no significant differences of the mutations in PreC G1896A and BCP A1762T,G1764A between patients with viral breakthrough (VBT) and without VBT, as well as patients with seroconversion and without seroconversion (P>0.05).②There were significant difference of mutations in G1896A between patients with and without YMDD mutants (P<0.05), and the mutation detection rate (9%) in patients with YMDD mutants was lower. ③There was significant difference of YMDD mutants between patients with VBT and without VBT (P<0.05). Conclusion The mutations in PreC G1896A and BCP A1762T, G1764A have not effects on VBT and seroconversion following Lamivudine therapy,and G1896A may reduce the appearance of YMDD. The YMDD mutants may be one of the factors that aggravate the damage of hepatocytes during the relapse.