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目的建立乙型肝炎病毒Ｐ基因区ＹＭＤＤ变异的检测方法，对用拉米夫定治疗５２周出现耐药的病人进行检测。方法从８８例治疗病人中选择１０例服用该药后ＨＢＶＤＮＡ转阴（＜１．６ｐｇ／ｍｌ），５２周时又反跳≥２０ｐｇ／ｍｌ的病人，用 ＰＣＲ后直接测序的方法，分别对 ０周和 ５２周标本进行 ＨＢＶ ＤＮＡ聚合酶活性区域的测序。结果 １０例服药５２周后ＨＢＶ ＤＮＡ反跳病人中７例测得ＨＢＶ ＹＭＤＤ变异。其变异分为两种类型：第一种类型为ＹＶＤＤ有５例，有核苷酸Ａ７４１→Ｇ，均伴有Ａ６６９→Ｃ的变异。第二种类型为ＹＩＤＤ有２例，有核苷酸Ｇ７４３→Ｔ，其中１例还有Ｔ７８１→Ｃ。结论少数病人在拉米夫定治疗过程中出现耐药，可能和ＨＢＶ ＹＭＤＤ变异有关。
Objective To establish a method to detect the YMDD mutation in the P gene region of hepatitis B virus (HBV), and detect the drug resistance in 52 weeks after treatment with lamivudine. Methods Eighty-eight patients were enrolled in this study. Ten patients underwent HBVDNA negative conversion (<1.6pg / ml) after taking this drug and anti-pounding more than 20pg / ml at 52weeks. Weeks and 52 week specimens were sequenced for HBV DNA polymerase activity. Results HBV YMDD mutation was detected in 7 out of 10 patients who took HBV DNA after 52 weeks. The variation is divided into two types: the first type is 5 cases of YVDD, a nucleotide A741 → G, are associated with A669 → C variation. The second type of YIDD in 2 cases, a nucleotide G743 → T, of which 1 cases there T781 → C. Conclusion A small number of patients in the process of lamivudine resistance occurred, may be related to HBV YMDD mutation.