慢性乙型肝炎患者持续应用恩替卡韦治疗3年的疗效

目的 研究恩替卡韦(ETV)治疗慢性乙型肝炎初治患者3年的病毒学、血清学和生物化学的应答情况,以评价其疗效.方法 本研究分两个阶段:第一阶段为ETV和拉米夫定(LAM)的双盲随机对照试验,各有258例和261例入选,分别用ETV 0.5 mg/d或LAM 100 mg/d口服,共96周.第二阶段:经96周治疗,患者如未达到综合应答(bDNA<0.7 mEq/ml,HBeAg阴转持续24周以上.ALT<1.25 X正常值上限)者,或出现病毒学突破或停药后复发者,继续服用ETV1.0 mg/d 48周.共有160例患者完成了连续3年的ETV治疗.持续变量的比较采用了基于线性回归模型的t检验.结果第一阶段结束时(96周),ETV和LAM治疗组患者的HBV DNA阴转率(HBV DNA<300拷贝/ml),ALT复常率和HBeAg血清转换率分别为:79%对比46%(P<0.01),96%对比92%(P=0.06)和21%对比23%.第二阶段:160例持续ETV治疗3年,第144周时,HBV DNA阴性(<300拷贝/ml)的比例为89%,ALT复常率86%,3年的累计HBeAg血清转换率为27%.耐药性:3例在96周时出现了基因型耐药,另有2例在第96～144周时出现了基因型耐药.ETV的耐受性良好,不良反应与LAM相似,但ETV组较少出现ALT反弹.结论 3年的临床试验表明ETV是强效的抗HBV药物,其抑制HBV复制和低耐药性明显优于LAM.

Results of 3 years of continuous entecavir treatment in nucleos(t)ide-naive chronic hepatits B patients

Objective To evaluate the virological,serological and biochemical outcomes of 3 years of entecavir(ETV)treatment in nucleoside-naive chronic hepatitis B patients.Methods This study was divided into two stages:Patients receiving either ETV 0.5 mg/d(n=258)or lamivudine(LAM)100 mg/d (n=261)entered the initial 96-week randomized,double blind,controlled efficacy study.Patients not achiering a consolidated response(HBV DNA<0.7 Meq/ml,ALT<1.25 times×ULN,and if HBeAg-positive at baseline,loss of HBeAg for≥24weeks),or those experienced viral breakthrough or relapse,entered a 48-week entecavir roilover study.Results 96 weeks after the treatment.79%of ETV treated and 46% of LAM treated patients had HBV DNA<300 copies/ml(P<0.0001),96% of ETV treated and 92% of LAM treated patients had normalized ALT(P=0.06).21% of ETV treated and 23%of LAM treated patients achieved HBeAg seroconversion.Among the 160 patients received continuous Etv for 144 weeks.89%had undetectable serum HBV DNA,86%showed ALT normalization,and 27%achieved HBeAg seroconversion.ETV resistance was rare:only 3 Patients showed ETV resistance 96 weeks after the treatment,and additional 2 patients developed ETV resistance during the following 48 weeks,genotyping indicated the ETV resistance was caused by gene mutation.Adverse event rates in ETV-treated patients were similar to those in LAMtreated patients.but fewer ALT flares were observed in ETV-treated patients.Conclusions This study demonstrates that ETV treatment results in long-term HBV suppression and ALT normalization in Chinese CHB patients,and is associated with low rate of drug resistance.