A randomized clinical trial of immunization with combined hepatitis A and B versus hepatitis B alone for hepatitis B seroprotection in hemodialysis patients

Abstract

Background: 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.

Study design: Prospective randomized controlled trial.

Setting & participants: Hepatitis B virus-seronegative hemodialysis patients with undetectable antibody levels at baseline.

Intervention: 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.

Outcomes: 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.

Measurements: Antibody response at months 3 and 7.

Results: 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.

Limitations: Lack of evidence of long-term protection.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00186836.