阿德福韦酯联合拉米夫定对拉米夫定耐药的慢性乙肝患者病毒学应答疗效研究

Virological response of adefovir dipivoxil and lamivudine combination therapy for patients with lamivudine-resistant chronic hepatitis B

目的 观察阿德福韦酯联合拉米夫定对拉米夫定耐药的慢性乙肝患者病毒学应答的效果.方法 使用免疫荧光定量PCR法检测HBV-DNA载量,实时荧光-PCR法检测HBV-YMDD变异,并采用全自动测序仪对PCR产物直接进行HBV-P基因测序,同时对46例拉米夫定耐药的慢性乙肝患者加用阿德福韦酯联合治疗48周,观察治疗期间所有患者的肝功能和病毒学相关指标.结果 46例拉米夫定耐药的慢性乙肝患者出现YMDD变异株35例;12周后HBV-DNA的转阴率为57.78%,ALT正常率58.90%;24周后HBV-DNA的转阴率为73.91%,ALT正常率78.26%;治疗48周后HBV-DNA的转阴率为80.43%,ALT正常率86.96%.拉米夫定联合阿德福韦酯治疗后各时段的原发性治疗无应答组HBV-DNA转阴率均低于病毒学突破组（均P＜0.05或0.01）;治疗48周后HBV-DNA转阴者的治疗前HBV-DNA平均载量低于未转阴者（P＜0.05）.结论 阿德福韦酯联合拉米夫定治疗拉米夫定耐药的慢性乙肝患者有效、安全,且原发性治疗无应答组HBV-DNA转阴率低于病毒学突破组,治疗前HBV-DNA水平较低者联合治疗后转阴率较高.

Objective To evaluate the virological response of adefovir dipivoxit （ADV） and tamivudine （LAM） combination therapy for patients with lamivudine-resistant chronic hepatitis B （CHB）. Methods Forty six patients with LAM-resistance CHB were treated by ADV and LAM combination therapy for 48 weeks. The HBVDNA was detected with FQ-PCR, HBV YMDD variation was detected with real-time PCR, and the PCR products of HBV P gene sequence was detected directly with automatic sequencer. The liver function and virological relevant index were evaluated during the treatment. Results There were 35 YMDD vari- ants in 46 patients with LAM-resistance CHB. At week12, 24 and 48 the negative rates of HBV DNA were 57.78%, 73.91% and 80.43% respectively; the alanine transaminase （ALT） recovery rates were 58.90%, 78.26% and 86.96%, respectively. The negative rate of HBV DNA in primary failure group was lower than in secondary failure group in patients treated with LAM after combination with ADV （P〈0.01 or P〈0.05）. Patients with high level of HBV DNA before combination therapy had lower negative rate of HBV DNA at week48 after combination therapy （P〈0.05）. Conclusion ADV and LAM combination therapy is effective and safe for patients with LAM-resistant chronic hepatitis B.