重组酵母乙型肝炎疫苗联合干扰素α-1b治疗慢性乙型肝炎的疗效  

Therapeutic effects of recombinant hepatitis B virus vaccine combined with interferon α-1b in patients with chronic hepatitis B

作　　者：徐启桓[1] 张晓红[1] 谢冬英[1] 李建国[1] 崇雨田[1] 杨林[1] 陆玮伦[1] 高志良[1] 田德英[2] 陈菊梅[3] 

机构地区：[1]中山大学附属第三医院感染科,广州510630 [2]华中科技大学同济医学院附属同济医院感染科 [3]解放军第三○二医院感染科

出　　处：《中华传染病杂志》2008年第3期163-167,共5页Chinese Journal of Infectious Diseases

摘　　要：目的 探讨重组酵母乙型肝炎疫苗治疗慢性乙型肝炎的疗效，确定合理剂量以用于更大样本的临床研究。方法 多中心、随机、双盲、安慰剂对照的临床试验。选择6个月内未经抗病毒治疗的慢性乙型肝炎患者216例，按1：1：1的比例采用分段随机方法分为90μg组、60μg组、安慰剂组，分别于0、2、6、10、14、18、22周肌内注射重组酵母乙型肝炎疫苗，每次90μg或60μg或安慰剂。所有患者均使用IFNα-1b50μg，每周3次，治疗24周。停药后观察24周。定期检测患者HBV DNA、HBeAg及肝功能。酶联免疫斑点试验（ELISPOT）法检测部分患者产生IFN-7的细胞数。结果 治疗24周时高剂量组、低剂量组和安慰剂组患者HBV DNA分别为（6．03±1．79）、（5．52±1．82）和（6．29±1．70）log10拷贝／mL（P=0．458）；停药后24周HBV DNA分别为（5．92±1．98）、（5．49±1．99）和（6．16±1．76）log10拷贝／mL（P=0．720）；治疗24周时，高剂量组、低剂量组及安慰剂组患者HBV DNA〈1×100拷贝／mL分别占30．4％、39．4％和20．8％，低剂量组与安慰剂组比较差异有统计学意义（P=0．015）；停药后24周，HBV DNA〈1×100拷贝／mL比例以低剂量组最高，但三组与治疗前比较差异无统计学意义（P=0．257）。停药后24周，HBV DNA转阴率分别为17．4％、25．4％和6．9％，差异有统计学意义（P-0．012）。治疗24周时及停药后24周，ALT复常率和HBeAg血清转换率以低剂量组最高，但三组比较差异无统计学意义。治疗24周时及停药后24周行ELISPOT试验显示，高剂量组、低剂量组ELISPOT阳性率比安慰剂组明显升高，差异有统计学意义（P〈0．05）。三组不良事件发生率相近，无一例发生药物相关的严重不良反应。结论重组酵母乙型肝炎疫苗治疗对HBV有一定的抑制作用，合理剂量是60μg。Objective To investigate the therapeutic effects of recombinant yeast hepatitis B virus（HBV） vaccine combined with interferon（IFN） α-1b and determine the rational dosage of HBV vaccine for the further clinical study with larger sample. Methods Two hundreds and sixteen patients with chronic hepatitis B（CHB） were enrolled in this randomized, multi-center, double-blinded and placebo-controlled clinical trial. All the subjects were not treated with antiviral drugs within 6 months and randomly divided into 90 μg, 60 μg and placebo groups with a ratio of 1 ： 1 ： 1. All the patients were intramuscularly administrated with 90 μg or 60 μg recombinant HBV vaccine or placebo at week 0, 2, 6, 10, 14, 18, 22, respectively. Meanwhile, they were also treated with IFNa-lh 50μg, 3 times a week for 24 weeks. All patients were followed up for 24 weeks after withdrawal of anti-HBV therapy. Serum HBV DNA level, HBeAg titer and liver function were monitored frequently. Interferon-7 secreting lymphoeytes were detected by Enzyme-linked immunospot（ELISPOT） in part of the patients. Results The serum HBV DNA levels were（6.03± 1.79）,（5.52± 1.82） and （6.29± 1.70） log10 eopy/mL at week 24 of treatment in high dose, low dose and placebo groups, respectively （P= 0.458）. And the serum HBV DNA levels were（5.92± 1.98）,（5.49± 1.99） and （6. 16± 1.76）1og10 copy/mL at week 24 after withdrawal of treatment, respectively（P = 0. 720）. The rates of patients whose HBV DNA 〈 1 〉 10^5 copy/mL in these three groups were 30.4%, 39. 4% and 20.8% at week 24 of treatment, respectively and there was significant difference between high dose group and low dose group（P = 0. 015）. The rate of patients whose HBV DNA 〈 1 〉 10^5 copy/mL at week 2t after withdrawal was highest in low dose group, but no significant differences before and after treatment in these three groups（P = 0. 257）. The HBV DNA negative rates were 17. 4%, 25.4% and 6. 9G in these three groups, respectively, which were sign

关 键 词：肝炎 乙型 慢性 肝炎病毒 乙型 肝炎疫苗 乙型 干扰素Α 临床试验 酵 母菌 

分 类 号：R512.62[医药卫生—内科学] R730.5[医药卫生—临床医学]