拉米夫定治疗慢性乙型肝炎患者乙型肝炎病毒YMDD变异的研究

目的探讨拉米夫定治疗1年后慢性乙型肝炎（CHB）患者发生YMDD基序变异的状况及其检测方法。方法采用荧光定量PCR法检测血清HBV DNA含量，荧光PCR法和变性高效液相色谱法检测HBV YMDD基序变异。结果61例CHB患者经过拉米夫定治疗1年后，40例（65．6％）HBV DNA阴转；在21例HBV DNA阳性患者中，10例为YMDD野生型，11例出现YMDD基序变异，变异率达18．0％（11／61）。在11例基序变异中，完全变异7例（63．6％），部分变异4例（36．4％）。在完全变异型中，YIDD变异型5例，YVDD变异型2例；在部分变异型中，YIDD变异型3例，YVDD变异型1例。结论CHB患者拉米夫定治疗1年后，出现较高的YMDD基序变异率。利用荧光PCR法结合变性高效液相色谱法检测基序变异，经济便捷，可作为CHB患者YMDD基序变异的常规监测。

YMDD mutations of hepatitis B virus in chronic hepatitis B patients treated with lamivudine

Objective To monitor the YMDD motif mutations of HBV in chronic hepatitis B (CHB) patients treated with Lamivudine and to develop a method for detection of the motif mutations.Methods The concentrations of serum HBV DNA was determined by fluorometric real-time PCR.YMDD motif mutations of HBV were detected by fluorometric PCR and denaturing high performance liquid chromatography (DHPLC).Results HBV DNA was detected in 21 out of 61 patients with CHB receiving one year therapy with Lamivudine.Of the 21 patients with HBV DNA, motif mutants were detected in 11 patients(18%), which included 7 complete mutants (63.6%) with YIDD in 5 and YVDD in 2, and 4 partial mutants (36.4%) with YIDD in 3 and YVDD in1.Conclusions A high rate of YMDD motif mutations may occur in CHB patients treated with Lamivudine. The combination of fluorometric PCR and DHPLC may be suitable for the detection of YMDD mutation.