乙型肝炎病毒YMDD自然变异与抗病毒治疗后变异特点

Study on spontaneous hepatitis B virus YMDD motif mutation and repulsive YMDD mutatant by lamivudine

目的了解未经拉米夫定抗病毒治疗的慢性乙型肝炎(CHB)患者和经拉米夫定治疗后的CHB患者乙型肝炎病毒基因组P区多聚酶YMDD变异情况,观察其特点。方法选择未接受过抗病毒治疗的CHB患者119例和经拉米夫定治疗后无明显效果的CHB患者30例,采用荧光标记杂交双探针聚合酶链反应熔解曲线法(FH-PCR-MC)对其血浆标本进行YMDD基因序列突变检测。结果119例未接受过抗病毒治疗的患者,变异检出率为19.3%(23/119),23例出现自然变异毒株的患者,其体内病毒均为变异株与野生株共生,且变异株为非优势株,变异株在总病毒量中所占的比例均在50%以下,变异类型以YVDD为主(20例)。30例经拉米夫定治疗的患者变异检出率为56.7%(17/30),17例阳性患者有11例患者体内病毒完全为变异毒株,仅6例患者为变异株与野生株共生,且变异株为优势株者占83.3%(5/6);在变异类型上YVDD占8例,居多;YVDD与YIDD同时阳性占3例。结论未经抗病毒治疗的CHB患者存在YMDD自然变异毒株,且变异株皆与野生株共生,变异株为非优势株。经拉米夫定治疗后的变异多数为完全变异,少数为变异株与野生株共生,且变异株大多为优势株。

Objective To investigate the natural mutation of hepatitis B virus（HBV） YMDD motif in patients with chronic hepatitis B （CHB） who dontt undergo lamivudine treatment and revulsive YMDD mutatant by lamivudine, and to observe its characteristic. Methods The HBV YMDD mutation was detected by fluorescent hybridization double probe PCR and melting curve assay （FH-PCR-MC） in 119 patients with CHB who were not treated with lamivudine and in 30 patients with CHB who were treated with lamivudine. Results Among 119 subjects with CHB who were not treated with lamivudine, spontaneous YMDD mutations were detected in 23 subjects （YVDD, YIDD and YVDD/YIDD for 20, 2 and 1 subject, respectively）, the YMDD mutant rate was 19.3 % （23/119）, and were all found to coexist with wild-type virus. The mutation strains weren＇t predominant, which proportion rate in total virus volume was below 50%. Among 30 cases with CHB who were treated with lamivudine, YMDD mutations were detected in 17 cases （YVDD, YIDD and YVDD/YIDD for 8, 6 and 3 respectively）, the YMDD mutant rate was 56.7 （17/30）, and only 6 cases were found to coexist with wild-type virus, the other 11 cases were revulsive YMDD mutation completely. Conclusion There are natural mutants of HBV YMDD in patients with CHB who aren＇t treated with lamivudine. And natural mutants of HBV YMDD were all found to coexist with wild-type virus; the YMDD mutants are not predominant. The great majority of YMDD mutants of HBV in patients with CHB who are treated with lamivudine are completely mutant, only a small number of YMDD mutations coexist with wild-type virus, and the great majority of YMDD mutants are predominant strains.