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


METHODS
Prospective randomized controlled trial.


METHODS
Hepatitis B virus-seronegative hemodialysis patients with undetectable antibody levels at baseline.


METHODS
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.


RESULTS
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.


METHODS
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.


CONCLUSIONS
Lack of evidence of long-term protection.


CONCLUSIONS
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.
Tung
Jennifer
J
St. Joseph's Healthcare, Hamilton, Ontario, Canada.
Carlisle
Euan
E
Smieja
Marek
M
Kim
Peter T
PT
Lee
Christine H
CH
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention / Q000379:methods; D011446:Prospective Studies; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment; D016896:Treatment Outcome; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
C075654:Engerix-B; D022362:Hepatitis A Vaccines; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D017778:Vaccines, Combined; C433226:twinrix