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目的 研究拉米夫定治疗慢性乙型肝炎时病毒发生ＹＭＤＤ变异对临床的影响及处理措施。方法 随机选择６６例病人用拉米夫定治疗（１００ｍｇ／ｄ）４８周，２０例病人服用安慰剂作对照共１２周，１２周结束后继续服用拉米夫定１００ｍｇ／ｄ共３６周。每隔４周检测一次血清ＨＢＶ ＤＮＡ、ＡＬＴ和ＹＭＤＤ变异，到治疗４８周为止。结果 治疗４８周结束时，共有１８例病人出现ＹＭＤＤ变异，变异率为２０．９％。其中２例在服药３６周时发生变异，其余１６例在服药４８周时发生。服药４８周时，变异者和非变异者的ＡＬＴ和ＨＢＶ ＤＮＡ的检测结果：变异者分别为（３６．２±４６．１）Ｕ／Ｌ和（１４．３ ± ２７．２）ｐｇ／ｍｌ，非变异者分别为（２０．４ ± １２．５）Ｕ／Ｌ和（２．５ ± ６．１）ｐｇ／ｍｌ，经Ｗｉｌｃｏｘｓｏｎ检验均有显著性差异（Ｐ＜０．０１）。发生变异的１８例病人继续服药，其中２例病人出现病情的急性发作，分别于８０周和９２周停药。经临床对症治疗，ＡＬＴ均恢复正常。其余１６例病人继续服药至１０４周。结论 拉米夫定治疗慢性乙型肝炎过程中，必须严密观察ＹＭＤＤ变异，一旦病人因ＹＭＤＤ变异出现病情急性发作，应停用拉米夫定。
Objective To study the clinical effect and treatment of YMDD mutation in lamivudine-treated chronic hepatitis B virus. Methods Sixty-six patients were randomized to lamivudine (100 mg / d) for 48 weeks, 20 patients received placebo for 12 weeks, and lamivudine 100 mg / d for another 36 weeks after the 12th week. Serum HBV DNA, ALT and YMDD mutations were tested every 4 weeks until 48 weeks of treatment. Results At the end of 48 weeks, a total of 18 patients showed YMDD mutation with a mutation rate of 20.9%. Two of these patients mutated at 36 weeks and the remaining 16 patients took medication at 48 weeks. At the 48th week of treatment, the ALT and HBV DNA of the mutants and non-mutants were: (36.2 ± 46.1) U / L and (14.3 ± 27.2) pg / ml, (20.4 ± 12.5) U / L and (2.5 ± 6.1) pg / ml, respectively. The Wilcoxson test showed significant difference (P <0.01). Eighteen patients who had mutated continued to take medication, two of whom experienced an acute episode of illness and were discontinued at weeks 80 and 92, respectively. After clinical symptomatic treatment, ALT returned to normal. The remaining 16 patients continued to take medication to 104 weeks. Conclusion Lamivudine in the treatment of chronic hepatitis B, YMDD mutation must be closely observed, once the patient due to YMDD mutation acute exacerbations, should be discontinued lamivudine.