目的 进一步了解HBV P基因结构与拉米夫定的疗效关系.方法 一步法扩增HBVP基因后进行测序,对比拉米夫定治疗应答,无应答和突破患者治疗前后血清HBV P基因结构的变化.结果 在无应答和突破患者中,2例B基因型和1例C基因型转变为B、C混合型HBV感染;1例患者血清HBV发生B→C基因型转换.3组中部分患者治疗前血清中检出YMDD变异株HBV,所有8例治疗无应答和突破患者在治疗过程中均出现YMDD变异.所有无应答患者治疗前后和突破患者突破时的血清HBV均出现rtL164V变异,而在应答者中未见.突破和无应答患者逆转录酶(rt)保守区还出现rt191L、rtK168R、rtH2ML、rtS256C 4个氨基酸替代.结论 YMDD基因序列变异不是产生拉米夫定临床耐药的惟一原因,rtL164V变异可能是一个新的与拉米夫定耐药相关的突变.%Objective To study the efficacy of lamivudine treatment in chronic hepatitis B patients affected by structures of HBV P-genes. Methods P genes of HBV isolated from sera were amplified by means of one-step PCR and then sequenced. The sequences of the P-genes from responders, primary non-responders and rebounders were compared before and after their lamivudine treatments. Results (1) Among the primary non- responders and rebounders,commixture genotype B and C was found in 2 parents with genotype B and in 1 patient with genotype C;genotype shift from B into C was also observed in one patient after lamivudine therapy. (2) During the course of the therapy YMDD mutation emerged in all 8 primary non-responders and rebounders, which existed in some patients of the 3 groups before their lamivudine treatment. (3) An ttL164V mutation in the reverse transcriptase region was observed in all primary non-responders before and after lamivudine therapy and also in rebounders when viral breakthrough occurred, which was not seen in the responders. (4) Four amino acid substitutions at rt91, rt168, rt234 and rt256 in the reverse transcriptase region were seen in the rebounders and primary non-responders. Conclusion YMDD mutation was not the only key point closely linked to HBV resistant to lamivudine therapy. RtLI64V may be a novel mutation correlated with lamivudine-resistance.
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