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成人乙型肝炎肝移植术后受者乙型肝炎疫苗主动免疫应答率与接种前CD4水平的相关性分析
DOI: 10.3969/j.issn.1001-5256.2021.08.012
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：王旭负责课题设计，数据整理，资料分析，撰写论文；许姗姗、荣义辉、蔡焕静参与收集数据，实施具体操作；王贵强负责拟定写作思路，指导撰写文章并最后定稿。
Rate of active immune response to hepatitis B vaccine in adult hepatitis B recipients after liver transplantation and its correlation with CD4 level before vaccination
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摘要:
目的 探究影响成人乙型肝炎肝移植术后受者乙型肝炎疫苗主动免疫应答率的主要临床影响因素。 方法 分析2019年5月—2020年11月北京大学国际医院15例乙型肝炎肝移植术后受者接种乙型肝炎疫苗的临床随诊资料，均为肝移植术后至少3年、接种前CD4水平300~800 cells/u的患者。每次予40 μg重组乙型肝炎疫苗(酿酒酵母)，接种频次按0、1、6、8个月间隔。4剂接种结束后抗-HBs≥100 mIU/L，并持续12周不衰减视为应答成功。应用Pearson相关性分析、Kendall相关性分析对接种前CD4水平及疫苗应答率的相关性进行分析；应用线性回归分析评价接种前CD4水平是否可预测疫苗主动免疫后抗-HBs水平；并应用logistic回归分析评价接种前CD4水平是否可预测疫苗能否应答。 结果 监测12周时，15例患者中6例应答，其中1例抗-HBs＞1000 mIU/L，5例抗-HBs≥100 mIU/L，继续监测至16周抗体滴度仍不衰减，乙型肝炎疫苗接种应答率为40%。6例应答者接种前CD4水平均≥592 cells/u，9例未应答者接种前CD4水平均≤500 cells/u。接种前CD4水平与乙型肝炎疫苗应答率呈强相关(Pearson相关性分析r=0.767，P=0.001；Kendall相关性分析r=0.717，P=0.001)。 结论 接种前的CD4水平是影响肝移植术后乙型肝炎疫苗应答率的关键因素。 Abstract:Objective To investigate the main clinical influencing factors for the rate of active immune response to hepatitis B vaccine in adult hepatitis B recipients after liver transplantation. Methods Analysis was performed for the clinical follow-up data of 15 hepatitis B recipients after liver transplantation who received hepatitis B vaccine in Peking University International Hospital from May 2019 to November 2020, and all patients received liver transplantation at least 3 years before and had a CD4 level of 300-800 cells/u before vaccination. Each dose of vaccination was 40 μg recombinant hepatitis B vaccine (Saccharomyces cerevisiae), with a total of 4 injections at 0, 1, 6, and 8 months. Anti-HBs ≥100 mIU/L after four injections which lasted for 12 weeks without attenuation was considered successful response. Pearson correlation analysis and Kendall correlation analysis were used to investigate the correlation between CD4 level before vaccination and vaccine response rate; a linear regression analysis was used to investigate whether CD4 level before vaccination could predict the titer of anti-HBs after active vaccine immunization; a logistic regression analysis was used to investigate whether CD4 level before vaccination could predict vaccine response. Results Of all patients at week 12 of monitoring, 6 patients had response, among whom 1 had an anti-HBs level of > 1000 mIU/L and 5 had an anti-HBs level of ≥100 mIU/L, and the antibody titer did not attenuate till week 16; the response rate of hepatitis B vaccine was 40%. The 6 patients with response had a mean CD4 level of ≥592 cells/u before vaccination, while the 9 patients without response had a mean CD4 level of ≤500 cells/u before vaccination. CD4 level before vaccination was strongly correlated with the response rate of hepatitis B vaccine (Pearson correlation analysis: r=0.767, P=0.001; Kendall correlation: r=0.717, P=0.001). Conclusion CD4 level before vaccination is a key clinical factor affecting the response rate of hepatitis B vaccine after liver transplantation. -
Key words:
- Hepatitis B /
- Liver Transplantation /
- Hepatitis B Vaccines /
- Antigens, CD4
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表 1 15例患者接种前CD4水平及完成乙型肝炎疫苗接种后抗-HBs的变化
病例 接种前CD4 (cells/u) 4剂全部接种完成后抗-HBs水平(mIU/L) 4周 8周 12周 16周 病例1 238 22.76(乙免) 病例2 279 69.28 55.73(乙免) 病例3 306 39.18(乙免) 病例4 324 55.68 67.90 58.12(乙免) 病例5 362 61.09 54.61(乙免) 病例6 378 39.65(乙免) 病例7 418 59.66 40.66(乙免) 病例8 448 78.70 65.01 30.84(乙免) 病例9 500 44.08(乙免) 病例10 592 133.05 235.43 291.50 350.01 病例11 598 170.07 162.69 180.17 167.47 病例12 663 109.37 96.23 114.10 128.33 病例13 670 105.11 144.23 154.95 188.18 病例14 678 220.39 367.10 210.80 236.89 病例15 803 489.47 798.01 ＞1000 ＞1000 注：“乙免”表示注射乙型肝炎免疫球蛋白。接种结束后，一旦抗-HBs持续低于60 mIU/L即需要接种乙型肝炎免疫球蛋白，此类患者视为无应答，且接种乙型肝炎免疫球蛋白后再次化验抗-HBs非疫苗接种后真实滴度，故不再继续监测抗-HBs。 
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