基线HBeAg水平对HBeAg阳性慢性乙型肝炎阿德福韦酯治疗52周疗效的预测价值

The predictive value of bsaeline HBeAg levels to the efficacy of 52 weeks treatment of adefovir dipivoxil in patients with HBeAg-positive chronic hepatitis B

目的评价HBeAg阳性慢性乙型肝炎患者的HBeAg基线水平对阿德福韦酯治疗1年疗效的预测价值。方法 98例HBeAg阳性、年龄18～60岁的慢性乙型肝炎患者进入研究。筛选时血浆HBV DNA定量≥1×106拷贝/ml,血清ALT水平1.5～10倍正常参考值上限,无其他原因引起的肝病。患者接受阿德福韦酯胶囊10mg/d治疗,共52周。定期随访,统一由专人检测HBV血清标志及HBV DNA。HBV血清标志物用Abbott试剂检测。HBeAg半定量采用样本值与截止值之比(s/co)表示,HBV DNA用实时荧光定量PCR方法检测,灵敏度为1×103拷贝/ml(3log10拷贝/ml)。结果阿德福韦酯治疗52周,HBV DNA水平较基线下降(3.63±1.26)log10拷贝/ml,HBV DNA检测不到率48.0%(47/98),ALT复常率为83.7%(82/98),HBeAg血清转换率为23.5%(23/98)。52周HBeAg血清转换组与无转换组患者的基线HBeAg水平分别为(251.9±117.3)s/co和(339.6±137.3)s/co(P=0.002),基线HBeAg水平≤350s/co者分别占78.3%(18/23)和36%(27/75,P<0.001),而两组基线HBV DNA水平和ALT水平无统计学意义。基线HBeAg≤350s/co(n=45)组和>350s/co(n=53)组比较,治疗12周两组HBV DNA检测不到率分别为35.6%和13.2%(P=0.009),HBeAg阴转率为22.2%和0(P<0.001),ALT复常率为55.6%和17.0%(P<0.001);治疗52周HBV DNA检测不到率为64.4%和34.0%(P=0.003),HBeAg血清转换率为42.2%和7.5%(P<0.001),ALT复常率为84.4%和83.0%。结论基线HBeAg水平对阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者的12周及52周疗效预测有一定的价值。基线HBeAg水平较低者能获得更好的早期病毒学应答和HBeAg血清转换率。

Objective To study the predictive value of baseline HBeAg levels to the efficacy of week 52 in patients with HBeAg-positive chronic hepatitis B treated with adefovir dipivoxil.Methods Ninety eight HBeAg-positive CHB patients with HBV DNA levels ≥1 × 106 copies/ml,ALT levels were 1.5 to 10 times of upper limits of normal（ULN） in serum were enrolled in the study.10 mg/d of adefovir dipivoxil were taken for 52 weeks.Line blood samples were collected and stored in-20 ℃ for detection HBV DNA and HBV markers.Semi-quantitation of HBeAg was performed using the ratio of sample value against the cut-off value（s/co） .HBV serum markers were detected using Abbott analysis kits and HBV DNA levels were assayed by real-time PCR technique（the sensitivity is 1000 copies/ml） by same technician.The efficacy of adefovir dipivoxil at week 52 were evaluated in patients with HBeAg levels ≤350 s/co and HBeAg levels 〉 350 s/co at baseline.Results At the end of study,HBV DNA levels decrease（3.63 ±1.26） log10 copies/ml,48%（47/98） were HBV DNA undetectable,HBeAg seroconversion rate was 23.5%（23 /98） and ALT normalization rate was 83.7%（82 /98） .The patients with HBeAg levels≤350 at baseline were61.7%（29/47）,34.5%（10/29） and27.3%（6/22） respectively in patients with HBV DNA undetectable,3 ～ 5log10copies/ml and 〉 5log10copies/ml at week 52.No significant differences of baseline HBV DNA levels were found,but baseline HBeAg levels（251.9 ± 117.3 vs.339.6 ± 137.6,P = 0.002） and rates of patients with HBeAg levels ≤ 350（78.3% vs.36.0%,P 〈 0.001） were different in subjects with HBeAg seroconversion compared to that with non-HBeAg seroconversion at week 52.After 12 weeks treatment with adefovir dipivoxil,35.6%（16 /45） and 13.2%（7 /53,P = 0.009） were HBV DNA undetectable,22.2%（10 /45） and 0（0 /53,P 〈 0.001） were HBeAg loss,55.6%（25 /45） and 17.0%（9/53,P 〈0.001） with normalized ALT in serum respectively in patients with HBeAg levels ≤350 and HBeAg levels 〉 350 at baseline.At the end of study,64.4%（29 /45） and 34.0%（18 /53,P = 0.003） were HBV DNA undetectable,42.2%（19 /45） and 7.5%（4 /53,P 〈 0.001） meet HBeAg seroconversion respectively in these two groups of patients.Conclusions Baseline levels of HBeAg in serum were correlated with the efficacy of adefovir dipivoxil in HBeAg-positive chronic hepatitis B.Baseline HBeAg levels ≤350 predict better virologic and biochemical responses at early stage,and higher rates of HBeAg seroconversion and HBV DNA undetectable at week 52.