拉米夫定联合阿德福韦酯治疗HBeAg阳性育龄期女性慢性乙型肝炎96周分析

Analysis on lamivudine plus adefovir for the treatment of women at reproductive age with e antigen-positive chronic hepatitis B:96-week study

目的探讨适合HBeAg阳性育龄期女性慢性乙型肝炎(CHB)抗病毒治疗的方法。方法对110例HBeAg阳性育龄期女性CHB,50例给予LAM 100 mg+ADV 10 mg联合口服治疗,1次/d;60例给予LAM 100 mg单药口服,1次/d。疗程均为96周。结果治疗至48、96周时,联合组有54%和82%%患者HBV DNA<1 000Copies/ml优于单药组(48.33%,68.33%),但差异无统计学意义(P>0.05);联合48周时有74%ALT复常优于单药组(61.67%),差异无统计学意(P>0.05);当至96周时,联合组90%患者ALT复常与单药组(75%),差异有统计学意义(P<0.05);48、96周时,联合组HBeAg血清阴转或转换率优于单药组(P<0.01)。联合组未出现病毒学突破和基因耐药发生患者,单药组有21.67%,16.67%和38.33%,30%的患者出现毒学突破和基因耐药(P<0.05)。结论 LAM与ADV初始联合治疗可明显改善HBeAg阳性育龄期CHB患者肝功能,降低单药引起的耐药问题,延长疗程可提高HBeAg阳性育龄期CHB患者HBeAg血清转换率。

Objective To evaluate the efficacy and safety of 96 - week combination therapy of lamivudine （LAM） plus adefovir （ADV） in women at reproductive age with e antigen -positive chronic hepatitis B. Methods 110 women at reproductive age with e antigen -positive chronic hepatitis B. were assigned to receive 100 mg LAM plus 10 mg ADV （n =50） or 100 mg LAM monotherapy （ n = 60） administrated orally once daily for 96 weeks. The efficacy results at week 48 and week 96 were compared in the two groups. Results The percentages of patients with HBV DNA less than 1000 copies/ml at week 48 （54%） and 96 （82%） in the combination therapy group were higher than those in the LAM monotherapy group （48% and 68% , respectively though the differences, there was no statistical significance （ P 〉 0.05 ）. Seventy - four percent （74%） of patients in the combination group achieved ALT normalization at week 48, compared with 62% in the LAM monotherapy group （P 〉 0.05）. By week 96, however, the ALT normalization rate was significantly higher in the combination therapy group （90% vs. 75% for combination vs. LAM therapies, respectively, P 〈 0.05 ）. The HBeAg seroeonversion rate was also significantly higher in the combination therapy group compared with the LAM monotherapy group （34% vs. 12% at week 48, and 46% vs. 22% at week 96; P 〈 0.01 for both comparisons）. No patient in the combination group experienced virological breakthrough or genotypic drug resistance, but there were 22% , 17% （at week 48） and 38% , 30% （at week 96） of patients in the LAM monotherapy experienced virological breakthrough or genotypic drug resistance. Conclusion Long - term combination therapy with LAM plus ADV in treatment - naive women at reproductive age with e antigen - positive chronic hepatitis B may suppress HBV replication, prevent disease progression, and significantly reduce the incidence of drug resistance.