拉米夫定治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎的早期病毒动态变化研究

目的 观察拉米夫定治疗乙型肝炎病毒e抗原(HBeAg)阳性慢性乙型肝炎的早期病毒动态变化.方法 多中心的临床试验,选择门诊及住院的HBeAg阳性慢性乙型肝炎患者,口服拉米夫定0.1 g,每日1次,共24周,应用实时聚合酶链反应(polymerase chain reaction,PCR)定量法检测其治疗前,治疗12 h、1 d,2 d,3 d、1周、2周、4周、12周、24周的血清乙型肝炎病毒(HBV)脱氧核糖核酸(DNA),并应用回归分析估计其病毒动力学参数.结果 共入选172例患者,年龄16～65(31±10)岁,男145例(84.3%),拉米夫定用药后12 h即出现明显的HBV DNA载量下降,平均下降0.45(范围:-1.85～3.86)lg(拷贝/m1),4例患者HBV DNA下降≥2 lg(拷贝/m1);2 d时进一步下降,与基线比较平均下降量1.20(范围:-1.21～4.41)lg(拷贝/ml);1周时继续下降,与基线比较,平均下降量2.01(范围:-0.17～5.79)lg(拷贝/ml).此后一直到24周,HBV DNA载量不断下降.24周时,平均下降量4.10(范围:-0.06～6.68)lg(拷贝/ml).游离病毒半衰期为2.57 d,受感染细胞的半衰期为63.0 d.结论 拉米夫定治疗HBeAg阳性慢性乙型肝炎能快速降低HBV病毒载量.

A clinical study of viral dynamic change in patients with hepatitis B e antigen positive chronic hepatitis B by iamivudine treatment

Objective To observe viral dynamic change in patients with HBeAg positive chronic hepatitis B by lamivudine treatment.Methods A multi-center clinical trial.Both outpatients and inpatients with HBeAg positive chronic hepatitis B have been administrated lamivudine 100 mg/d for 24 weeks.To detect the hepatitis B virus(HBV)deoxyribonucleic acid(DNA)levels of the baseline,12hours,1 day,2 days,3 days,1 week,2 weeks,4 weeks,12 weeks,24 weeks after lamivudine treatment by real time polymerase chain reaction(PCR).To estimate the parameters of viral dynamics through regression analysis.Results 172 patients were enrolled,145 male,30.8±9.7(16-65)years old Significant decrease of HBV DNA level occurred 12 hours after administration,the average decrease was 0.45 lg(copies/ml),maximum was 3.86 lg(copies/ml),4 patients decreased not less than 2 lg(copies/ml).On day 2 and 7,the average decrease was 1.20 lg(copies/ml)and 2.01 lg(copies/ml),maximum was 4.41 lg(copies/ml)and 5.79 lg(copies/ml),respectively.Then HBVDNA level continued decreasing until week 24.24-week administration of lamivudine cause 4.10 lg(copies/ml)decrease of HBV DNA averagely and 6.68 lg (copies/ml)mostly.Half life of free virion was 2.57 days.Half life of infected hepatocyte was 63.0 days.Conclusion Lamiviudine could rapidly decrease the HBVDNA level of patients with HBeAg positive chronic hepatitis B rapidly.