Peces R, de la Torre M, Alcázar R, Urra J M
Services of Nephrology and Immunology, Hospital Alarcos, Ciudad Real, Spain.
Am J Kidney Dis. 1997 Feb;29(2):239-45. doi: 10.1016/s0272-6386(97)90036-6.
Hepatitis B vaccine is effective in producing protection against hepatitis B virus (HBV) infection in hemodialysis (HD) patients, but the antibody response is variable. To identify those factors implicated in the vaccine response, in a prospective study over a 24-month period, we vaccinated 80 seronegative patients on HD (group A) and monitored clinical, biochemical, and immunologic parameters. The protective immunity acquired by vaccination was compared with that developed through HBV infection in 22 age-matched HD patients (group B). The anti-HBs antibody-seronegative patients followed a four-dose vaccination schedule (0, 1, 2, and 6 months) with 40 microg DNA-recombinant hepatitis B vaccine. One month after vaccination, 77.5% of the patients had seroconverted, and 72.5% achieved high antibody response, whereas 22.5% were nonresponders. Patients aged younger than 40 years seroconverted 100%; those aged 40 to 60 years, 75% (P < 0.01); and patients older than 60 years, 74% (P < 0.001). No differences between responders and nonresponders concerning sex, time on HD, HD dose, nutritional status, hemoglobin level, HD membrane, iPTH level, calcitriol treatment, or number of transfusions during vaccination were found. The presence of other factors, such as recombinant human erythropoietin (rHuEPO) therapy or hepatitis C virus (HCV) infection, did not significantly influence antibody responses to hepatitis B immunization. A greater frequency of DR3 (53.8% v 25.7%, P < 0.05), DR7 (53.8% v 18.6%, P < 0.01), and DQ2 (76.9% v 44.1%, P < 0.05), and a lesser frequency of A2 (7.7% v 37.2%, P < 0.05) were found in nonresponders compared with responders. Eighteen months after vaccination, the analysis showed similar antibody titers but lower seroconversion rates in group A as compared with group B. In conclusion, unresponsiveness to hepatitis B vaccine in HD patients was related to factors such as older age, the presence of DR3, DR7, and DQ2, and the absence of A2 alleles. Although the seroprotection produced by the vaccine was less than that achieved through natural HBV infection, our protocol of vaccination was sufficiently immunogenic and provided lasting protection.
乙肝疫苗对血液透析（HD）患者预防乙肝病毒（HBV）感染有效，但抗体反应存在差异。为确定与疫苗反应相关的因素，在一项为期24个月的前瞻性研究中，我们为80名HD血清阴性患者（A组）接种疫苗，并监测临床、生化和免疫参数。将接种疫苗获得的保护性免疫与22名年龄匹配的HD患者（B组）通过HBV感染产生的免疫进行比较。抗-HBs抗体血清阴性患者按照0、1、2和6个月的四剂接种方案，接种40微克DNA重组乙肝疫苗。接种后1个月，77.5%的患者发生血清转化，72.5%的患者产生高抗体反应，而22.5%的患者无反应。40岁以下患者血清转化率为100%；40至60岁患者为75%（P<0.01）；60岁以上患者为74%（P<0.001）。在性别、HD时间、HD剂量、营养状况、血红蛋白水平、HD膜、iPTH水平、骨化三醇治疗或接种期间输血次数方面，有反应者和无反应者之间未发现差异。其他因素，如重组人促红细胞生成素（rHuEPO）治疗或丙型肝炎病毒（HCV）感染，对乙肝免疫的抗体反应无显著影响。与有反应者相比，无反应者中DR3（53.8%对25.7%，P<0.05）、DR7（53.8%对18.6%，P<0.01）和DQ2（76.9%对44.1%，P<0.05）的频率更高，而A2（7.7%对37.2%，P<0.05）的频率更低。接种疫苗18个月后，分析显示A组与B组相比抗体滴度相似但血清转化率较低。总之，HD患者对乙肝疫苗无反应与年龄较大、存在DR3、DR7和DQ2以及缺乏A2等位基因等因素有关。尽管疫苗产生的血清保护作用小于自然HBV感染，但我们的接种方案具有足够的免疫原性并提供持久保护。
