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目的评价国产阿德福韦酯(优贺丁)片10mg/d治疗HBeAg阳性的中国慢性乙型病毒性肝炎患者48周的疗效和安全性。方法采用多中心、随机、双盲、安慰剂平行对照的研究设计。前12周双盲阶段,240例患者按2:1的比例随机进入优贺丁组(160例)或安慰剂组(80例);12～36周,所有患者均接受开放的优贺丁治疗;36～48周原双盲阶段中接受优贺丁治疗的患者重新按1:3的比例随机分入安慰剂组(A组,40例)或继续优贺丁治疗组(B组,120例),而第一阶段服用安慰剂的患者(C组,80例)在此阶段将继续接受优贺丁治疗。主要疗效评估指标为血清HBV DNA的变化情况,次要疗效评估指标包括:丙氨酸转氨酶(ALT)的复常率、HBeAg阴转率和HBeAg的血清转换率。结果12周时,A、B组HBV DNA中位数水平较基线分别降低2.43和2.54log10拷贝/ml,均显著好于C组(P<0.05);36周时,A、B、C组HBV DNA水平中位数较基线分别降低了3.57、3.24和3.29log10拷贝/ml;48周时,B、C组患者HBVDNA中位数水平分别较基线时下降3.58和3.38log10拷贝/ml,而A组则恢复到7.37log10拷贝/ml。12周时,A、B组HBV DNA转阴率分别为17.50%和25.83%,显著高于C组的1.25%(P分别均<0.01);36周时,A、B、C组HB VDNA转阴率分别为37.50%、26.67%和28.75%,三组间无显著差异(P=0.45);48周时,B、C组HBV DNA转阴率持续升高达到34.17%和31.25%,而A组则降为7.50%。48周时,B、C组ALT复常率持续升高达75.25%和64.06%,A组则由36周时的75.68%降为28.57%;B组HBeAg转阴率和血清转换率分别为6.42%和4.55%。安全性方面,研究期间各治疗组血清肌酐及血磷值平均水平同基线相比无变化。结论优贺丁片10mg/d剂量治疗48周HBeAg阳性的中国慢性乙型肝炎患者有效和安全。
Objective To evaluate the curative effect and safety of domestic adefovir dipivoxil (10 g / d) for 48 weeks in patients with HBeAg-positive chronic hepatitis B in China. Methods A multicenter, randomized, double-blind, placebo-controlled study was designed. In the first 12 weeks of the double-blind phase, 240 patients randomized to either the Euggestan group (160 patients) or the placebo group (80 patients) at a 2: 1 ratio. All patients received open etanercept treatment for 12 to 36 weeks ; Patients in the original double-blind stage of 36-48 weeks who received euqutin therapy were randomly assigned to placebo (group A, n = 40) or continuation of euggestine (group B, n = 120) at a 1: Patients in the first phase of placebo (group C, n = 80) will continue treatment with euqethin at this stage. The main efficacy indicators for the change of serum HBV DNA, secondary efficacy evaluation indicators include: alanine aminotransferase (ALT) normalization rate, HBeAg negative rate and HBeAg seroconversion rate. Results At 12 weeks, the median HBV DNA levels in group A and group B were 2.43 and 2.54 log10 copies / ml lower than those in group C, respectively (P <0.05). At 36 weeks, HBV DNA in group A, B and C Median DNA levels were 3.57, 3.24 and 3.29 log10 copies / ml lower than baseline, respectively; at 48 weeks, the median HBV DNA levels in patients in groups B and C were 3.58 and 3.38 log10 copies / ml, respectively, compared with baseline, while those in group A Then returned to 7.37log10 copies / ml. At 12 weeks, the HBV DNA negative rates in groups A and B were 17.50% and 25.83%, respectively, which were significantly higher than 1.25% in group C (P <0.01, respectively). At 36 weeks, The negative rates were 37.50%, 26.67% and 28.75% respectively, with no significant difference among the three groups (P = 0.45). At 48 weeks, the HBV DNA negative rates in groups B and C continued to increase to 34.17% and 31.25% The group dropped to 7.50%. At 48 weeks, the ALT normalization rates in groups B and C continued to increase by 75.25% and 64.06%, respectively, from 75.68% in 36 weeks to 28.57% in group A; the rates of HBeAg negative conversion and seroconversion in group B were 6.42% And 4.55%. In terms of safety, the mean serum creatinine and phosphorus levels in each treatment group during the study period did not change from baseline. Conclusions EHV 10 mg / d is effective and safe for HBeAg-positive patients with chronic hepatitis B in China for 48 weeks.