乙型肝炎病毒YMDD联合前C变异及其临床意义

目的：研究拉米夫定治疗过程中乙型肝炎病毒（HBV）前C区，P区YMDD基序变异及其对疗效的影响。方法：对5例拉米夫定（100mg/d)治疗过程中HBeAg血清转换而HBV DNA仍阳性的慢性乙型肝炎患者，采用聚合酶链反应（PCR）产物直接测序方法分析HBV前C、P区的基因序列，结果：5例患者前C区均发现有G1896A变异，其中3例HBeAg血清转换前未发现此变异，2例已有此变异，同时5例患者在拉米夫定治疗后检测出YMDD变异，变异类型均为M5521，其中有1例在出现M5521变异40周后变为M552V变异，有2例M5521联合L528M变异，5例患者中有1例治疗无反应，另4例在治疗过程中HBV DNA突发，结论：拉米夫定治疗过程中YMDD变异的出现可导致HBV DNA突发，而前C区G1896A变异可致HBeAgbe阴转，因此在治疗过程中出现HBeAg血清转换后需结合HBV DNA检测，排除前C区变异的可能。

Emergence of the pre C and YMDD mutations and its clinical significance during lamivudine treatment

Objective To explore pre C and YMDD motif mutant of hepatitis B virus during lamivudine therapy. Methods From five chronic hepatitis B patients with serum HBeAg seroconversion but HBV DNA positive by polymerase chain reaction(PCR) following lamivudine therapy, sequences of the pre C and P genes of hepatitis B virus were analyzed by direct PCR product sequencing methods. Results All the five patients were observed to have G to A variations at nucleotide 1896. However, such mutations were observed only in 2 of the 5 patients before HBeAg seroconversion emerged. Meanwhile YMDD mutations were found in all the five patients during lamivudine therapy three of which were M552I mutants, two were M552I associated with L528M. One of the five patients had no reaction to the therapy, four had HBV DNA breakthrough during therapy. Conclusions The mutants of pre C associated with YMDD mutations may arise in the patients with HBeAg seroconversion and positive HBV DNA during the treatment of lamivudine. HBV DNA should be detected in the patients with HBeAg seroconversion to exclude the pre C mutation.