拉米夫定治疗慢性乙型肝炎疗效观察及YMDD变异分析  

Clinical Effect of Lamivudine in Treating Chronic Hepatitis B and YMDD Mutation

作　　者：李红梅[1] 刘映霞[1] 刘书香[1] 邱红梅[1] 蒋孝华[1] 唐武成[1] 

机构地区：[1]南华大学附属第一医院肝病研究中心,湖南衡阳421001

出　　处：《医学临床研究》2006年第4期512-515,共4页Journal of Clinical Research

摘　　要：【目的】探讨拉米夫定(3TC)对慢性乙型肝炎(CHB)的治疗效果,以及乙型肝炎病毒(HBV)聚合酶酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸(YMDD)基序变异对3TC疗效的影响。【方法】检测分析58例接受3TC治疗的CHB患者治疗前后血清标志物HBVDNA、ALT、HBVM的变化,以及治疗后HBVYMDD变异情况。【结果】3TC治疗HBeAg阴转率为40.38%,eAg/抗-e血清转换率为28.85%,HBVDNA阴转率为74.14%,ALT复常率为77.59%。随着疗程的延长,有65.12%病例出现反跳。检测出23例患者发生YM-DD变异,变异发生率为39.66%,且以YVDD型变异为主要形式。YMDD变异与3TC治疗疗程相关;治疗前HBV病毒载量与治疗后YMDD变异的发生可能无相关性(P>0.05);HBeAg阳性与HBeAg阴性者YMDD变异发生率可能无明显差异(P>0.05)。【结论】3TC治疗CHB的短期疗效好,但随着疗程的延长,会出现病毒耐药,3TC耐药与YMDD变异密切相关。YMDD变异耐药株的产生可能与肝炎复发以及肝脏损害加重相关。在3TC治疗过程中,可能还存在HBV基因其他位点的变异而引起耐药。[Objective]To study the effects of lamivudine in treating chronic hepatitis B （CHB）, and the condition of the tyrosine-methionine-aspartic acid-aspartic acid （YMDD） mutation in hepatitis B virus （HBV） polymerase gene after lamivudine therapy. [Methods]Fifty eight CHB cases were analyzed with HBV DNA, ALT and HBVM before and after lamivudine treatment, the HBV YMDD mutation was also studied after the treatment. [Results]After lamivudine treatment, HBeAg negative rate was 40.38%, eAg/ anti-e serum conversion rate was 28. 85%, the HBV DNA negative rate was 74.14%, the ALT recovery rate was 77.59%. Along with the extension of the lamivudine treatment, 65.12% cases rebounded. YMDD mutation was found in 23 cases, and was the main form in mutation types. The period of treatment was related with the mutation of YMDD, no relativity was found between ex-treatment HBV carry and YMDD mutation （ P 〉0. 05）. No difference was found in YMDD mutation rate between HBeAg positive cases and HBeAg negative cases （ P〉 0.05）. [Conclusion]Lamivudine treatment is effective on CHB in shortterm, but along with the period extension, the virus would be drug fast with lamivudine by mutation of YMDD. The mutation of YMDD might be responsible for the hepatitis relapse or aggravating liver injures. The drug fast of lamivudine in the virus is also caused possibly by mutation in other HBV gene sites.

关 键 词：肝炎 乙型 慢性/药物疗法 拉米夫定/治疗应用 变异(遗传学) 

分 类 号：R512.62[医药卫生—内科学]