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目的 用基因芯片技术检测拉米夫定耐药的慢性乙型肝炎患者乙型肝炎病毒 (HBV)DNAP区YMDD基序变异情况 ,探讨变异对临床的影响 ,为疗效预测及制定进一步治疗措施提供依据。方法 取 4 0例临床考虑拉米夫定耐药患者的血清 ,用基因芯片的方法检测血清样本YMDD基序变异情况。观察变异检测阳性患者反跳时的丙氨酸氨基转移酶 (ALT)水平及血清转换情况。结果 4 0例患者血清标本中 ,用基因芯片法检测HBVDNAP区YMDD变异 ,YMDD变异阳性标本 2 7例 ,总变异检出率为 6 7.5 % (2 7/ 4 0 )。单纯YMDD变异 5例 ,YMDD变异株与野生株混合存在 2 2例。在变异类型中 ,YIDD变异 4例 ;YVDD变异 16例 ;YIDD与YVDD混合变异 7例。血清HBVDNA反跳时YMDD变异组ALT正常者有 13例。 4 0例患者中有 3例发生血清转换 ,在YMDD变异检测阳性者中有 1例发生血清转换。结论 在拉米夫定治疗过程中出现血清HBVDNA反跳时 ,多数患者血清中可以检出YMDD变异。反跳时变异株大多与YMDD野生株以共生形式存在 ,尤以YVDD变异为多 ,这可能是耐药变异出现后继续服用拉米夫定仍然有效的原因。用基因芯片技术能较好地检测YMDD变异情况 ,并能检测到患者体内变异株与野生株存在形式。
Objective To detect the mutation of YMDD motif in hepatitis B virus (HBV) DNAP region in patients with lamivudine-resistant chronic hepatitis B by gene chip technique and to explore the effect of mutation on the clinical effect, so as to provide evidence for the prediction of therapeutic effect and further treatment measures . Methods Forty-four patients with lamivudine-resistant patients were enrolled in this study. The mutation of YMDD motif in serum samples was detected by gene chip. To observe the level of alanine aminotransferase (ALT) and serum conversion in patients with positive mutation detection. Results Serum samples from 40 patients were detected by DNA microarray. The YMDD mutation in HBVDNAP region was detected by PCR. The positive rate of YMDD mutation was 27.7%. The overall mutation detection rate was 67.5% (27/40). There were 5 cases of simple YMDD mutation and 22 cases of YMDD mutant mixed with wild type. Among the types of mutation, YIDD mutation was found in 4 cases, YVDD mutation in 16 cases, YIDD and YVDD in 7 cases. Serum HBVDNA rebound YMDD mutation group of normal ALT in 13 cases. Seroconversion occurred in 3 out of 40 patients and seroconversion in 1 of the positive YMDD mutations. Conclusion When serum HBVDNA rebound occurs during lamivudine treatment, YMDD mutation can be detected in most patients’ serum. Most of the mutants at rebound exist with the wild-type YMDD strains in the form of coexistence, especially the variation of YVDD is much, which may be the reason why the resistance mutation continues after taking lamivudine. Gene chip technology can better detect YMDD mutation, and can detect the presence of mutant and wild-type strains in patients.