168例耐拉米夫定慢乙肝病毒的分布及临床研究

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：168例耐拉米夫定慢乙肝病例中4例为预存在突变株；164例为拉米夫定应用期间产生的耐药株，对其中病毒载量≥104拷贝／ml的128例耐药株作YMDD变异检测，YVDD变异42株、YIDD变异20株、其它变异66株。分属“指导意见”中临床情况良好，较轻与恶化的例数为8：108：12。在非YMDD变异组中的病毒载量中、高等级的例数分别是56，10，而YMDD变异组中、高等级的例数是45，4，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。

Distribution of lamivuidine- resistant variants in hepatitis B virus

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.