St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Am J Kidney Dis. 2010 Oct;56(4):713-9. doi: 10.1053/j.ajkd.2010.04.015. Epub 2010 Jul 13.
The Centers for Disease Control and Prevention recommend immunizing susceptible high-risk groups, such as hemodialysis patients, against hepatitis B virus. However, hemodialysis patients may not develop seroprotective antibodies despite receiving high doses of the vaccine. Recent reports indicate that combined vaccination against hepatitis B and hepatitis A viruses may improve the immunogenicity of hepatitis B vaccine in healthy individuals, but the effectiveness of this strategy in hemodialysis patients is unknown.
Prospective randomized controlled trial.
SETTING & PARTICIPANTS: Hepatitis B virus-seronegative hemodialysis patients with undetectable antibody levels at baseline.
Intramuscular administration of Twinrix (inactivated hepatitis A virus [720 ELISA units] and purified hepatitis B virus surface antigen [20 μg]; GlaxoSmithKline) and Engerix-B (purified hepatitis B virus surface antigen [20 μg]) at 0, 1, and 6 months plus Engerix-B, 40 μg, at month 2 (intervention arm) or Engerix-B, 40 μg, at 0, 1, 2, and 6 months (control arm). Both groups received a total dose of 160 μg of hepatitis B antigen.
The primary outcome was the difference in seroprotection rates at 7 months, defined by antibody titers >10 mIU/mL. The secondary outcome was frequency of adverse events.
Antibody response at months 3 and 7.
96 patients were enrolled, and 73 completed the investigation. At 3 months, there was no difference in the groups' seroprotection rates (25% vs 27%; P = 0.4). At the completion of the vaccination series, using per-protocol analysis, 27 of 40 (68%) and 16 of 33 (49%) had antibody titers >10 mIU/mL in the treatment and control groups, respectively (P = 0.05; RR, 1.4; absolute abatement, 19%). Intention-to-treat analysis showed 58% and 38% seroprotection rates in the treatment and control groups, respectively (P = 0.02; RR, 1.5; absolute abatement, 20%). There was no difference in adverse events.
Lack of evidence of long-term protection.
Vaccination of hemodialysis patients with a combined hepatitis A and hepatitis B regimen resulted in a statistically significant and clinically important improvement in seroprotection against hepatitis B virus compared with hepatitis B monovalent vaccine.
疾病控制与预防中心建议对易感高危人群（如血液透析患者）进行乙型肝炎病毒免疫接种。然而，血液透析患者在接受高剂量疫苗后可能无法产生保护性抗体。最近的报告表明，联合接种乙型肝炎和甲型肝炎病毒疫苗可能会提高健康人群乙型肝炎疫苗的免疫原性，但这种策略在血液透析患者中的有效性尚不清楚。
前瞻性随机对照试验。
乙型肝炎病毒血清学阴性、基线时抗体水平不可检测的血液透析患者。
肌肉内注射 Twinrix（灭活甲型肝炎病毒[720 ELISA 单位]和纯化乙型肝炎病毒表面抗原[20μg]；葛兰素史克）和 Engerix-B（纯化乙型肝炎病毒表面抗原[20μg]），在 0、1 和 6 个月时加用 Engerix-B，40μg，在 2 个月时（干预组）或 Engerix-B，40μg，在 0、1、2 和 6 个月时（对照组）。两组均接受 160μg 乙型肝炎抗原的总剂量。
主要结局为 7 个月时的血清保护率差异，定义为抗体滴度>10 mIU/mL。次要结局为不良事件的频率。
第 3 个月和第 7 个月的抗体反应。
共纳入 96 例患者，73 例完成了调查。3 个月时，两组的血清保护率无差异（25%对 27%；P=0.4）。在完成疫苗系列接种后，根据方案分析，治疗组和对照组分别有 27/40（68%）和 16/33（49%）的患者抗体滴度>10 mIU/mL（P=0.05；RR，1.4；绝对减少，19%）。意向治疗分析显示，治疗组和对照组的血清保护率分别为 58%和 38%（P=0.02；RR，1.5；绝对减少，20%）。两组不良事件无差异。
缺乏长期保护的证据。
与乙型肝炎单价疫苗相比，血液透析患者联合接种甲型肝炎和乙型肝炎疫苗方案可显著提高乙型肝炎病毒的血清保护率，具有统计学意义和临床意义。
