168例耐拉米夫定慢乙肝病毒的分布及临床研究

Distribution of lamivuidine- resistant variants in hepatitis B virus

目的 :观察耐拉米夫定乙肝病毒耐药株的分布、慢性乙型病毒性肝炎的临床表型。方法 :用 PCR产物直接测序检测拉米夫定治疗慢乙肝前后的 YMDD变异 ,分析耐拉米夫定耐药株的分布及临床表型。结果 :16 8例耐拉米夫定慢乙肝病例中 4例为预存在突变株 ;16 4例为拉米夫定应用期间产生的耐药株 ,对其中病毒载量≥ 10 4拷贝/ ml的 12 8例耐药株作 YMDD变异检测 ,YVDD变异 4 2株、YIDD变异 2 0株、其它变异 6 6株。分属“指导意见”中临床情况良好 ,较轻与恶化的例数为 8∶ 10 8∶ 12。在非 YMDD变异组中的病毒载量中、高等级的例数分别是 5 6 ,10 ,而 YMDD变异组中、高等级的例数是 4 5 ,4 ,临床表型重的病例数非 YMDD变异组为 10例 ,而 YMDD变异组为 2例。结论 :慢性乙型肝炎的 YMDD变异株可以是预存在的 ,部分 YMDD变异株可能是由于因耐拉米夫定而选择性保留并成为优势株。非 YMDD变异组的临床表型重于 YMDD变异组。

Objective: To observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis. Methods: Using direct sequencing,YMDD(tyrosine-methionine-aspartate-aspartate)variants in patients with chronic HBV were detected before and during treatment with lamivudine. A statistical analysis of the distribution of HBV strains resistant to lamivudine was performed. Results: Four va- riant strains existed in patients before lamivudine treatment,128 variant resistant strains were noted after 6 mouths of lamivudine treatment including 42 YVDD(valine) variants,20 YIDD(isoleusine) variants and 66 non-YMDD variants. According to the hepatitis severity,8 patients were mild,108 moderate and 12 severe. Viral loading was higher and clinical types were more severe in no-YMDD variants. Conclusion: Variant strains including strains resistant to lamivudine exist naturally before lamivudine treatment,but lamivudine-resistant ones become more dominant after treatment. Liver inflammation is more severe in non-YMDD group.