拉米夫定治疗慢性乙肝的疗效及乙肝病毒YMDD变异的研究  

A Study on the Therapeutic Efficacy of Lamivudine in Chronic Hepatitis B and HBV YMDD Mutants

作　　者：齐青松[1] 陈仕彬[1] 杨茜[1] 易冬英[1] 

机构地区：[1]南昌大学第一附属医院感染科,江西南昌330006

出　　处：《江西医学院学报》2005年第5期42-45,49,共5页Acta Academiae Medicinae Jiangxi

摘　　要：目的评价拉米夫定治疗慢性乙肝病人的1年疗效、乙肝病毒YMDD变异率、变异与治疗前HBV-DNA、ALT水平的联系。方法治疗组按入选标准随机选择32例慢性乙型肝炎患者给予拉米夫定100 mg/d并随访1年,并于治疗开始后3、6、9、12个月检测肝功能、HBV-M、HBV-DNA、YMDD变异。对照组随机选择36例从未接受抗病毒治疗的HBV-DNA阳性、ALT异常的慢性乙型肝炎患者,检测YMDD变异株。结果①拉米夫定治疗一年,HBV-DNA转阴率71.88%(23/32),HBeAg/HBeAb血清转换率18.52%(5/27),ALT复常率62.5%(20/32);治疗前及治疗12个月后ALT水平分别为132.59±66.07、49.78±27.94,治疗前后差别有统计学意义(P<0.001)。②治疗组在治疗前未发现YMDD变异,治疗6个月发现2例YMDD变异,变异率6.25%,治疗12个月发现5例YMDD变异,变异率15.63%;对照组36例从未接受抗病毒治疗的慢性乙型肝炎病人中检测出2例YVDD变异株与野生株共存。③治疗前ALT<3×ULN组及≥3×ULN组YMDD变异率分别为11.76%、20.00%,两组差别无统计学意义(P=0.645);治疗前HBV-DNA<106copies/mL组及≥106copies/mL组YMDD变异率分别为5.88%、26.67%,两组差别无统计学意义(P=0.161)。结论拉米夫定能迅速抑制乙肝病毒复制、改善肝功能;治疗前HBV-DNA水平及ALT水平不足以预见YMDD变异的发生;乙肝病毒YMDD变异株存在于未使用拉米夫定的慢性乙肝患者中,建议在抗病毒治疗前对YMDD变异进行常规检测。Objective To evaluate three aspects of lamivudine including its clinical efficacy,incidence rate of YMDD mutant,and relationship between the mutation and pre-treatment levels of HBV DNA and ALT. Methods （GROUP Ⅰ）Thirty-two patients with chronic hepatitis B were randomly selected to treat with lamivudine. The liver function and HBV virology including HBV-DNA level, HBV marker,YMDD mutant were tested every three months. （GROUP Ⅱ）Other 36 patients with chronic hepatitis B were randomly selected as control without treatment. YMDD mutant was tested. Results The clinical efficacy of lamivudine including the negative conversion rate of serum HBV-DNA, the seroconversion rate of HBeAg/HBeAb and normalization rate of ALT were 71.88% （23/32）, 18.52 % （5/27）, 62.5 % （20/32） respectively in one year. The baseline ALT was 132. 59±66.07U/L and was 49.78±27. 94 U/L in one year. The ALT level between them showed statistically significant diffirence（P〈0. 001）. No YMDD mutation was detected before therapy in group I. Two YMDD mutants were detected in 6 months and fiver YMDD mutants in one year in group Ⅰ. The rate of mutation were 6. 25% and 15.63% respectively. Two YMDD mutants were detected in GROUP II. The rate of mutation in the group with 〈3 × ULN of and in that with ≥3 × ULN of baseline ALT were 11.76% and 20. 00%,respectively（P= 0. 645）. The rate of mutation were 5.88% and 26.67%in 〈10^6 copies/mL group and ≥10^6 copies/mL group of baseline HBV-DNA respectively（P = 0. 161）. No statistically significant diffirence was showed. Conclusion Lamivudine therapy can prohibit HBV-DNA replication in patients with chronic hepatitis B,and improve liver function, The ALT level and the HBV-DNA level of pre-therapy are not enough to predict the YMDD mutation. The mutant strains of YMDD are present in lamivudine-untreated patients with chronic hepatitis B. We suggest that the YMDD mutant should be detected in patients with chronic hepatitis B routinely before antivirus therapy.

关 键 词：拉米夫定 YMDD变异 慢性乙型肝炎 

分 类 号：R512.62[医药卫生—内科学]