title: Hepatitis B virus vaccine in chronic kidney disease: improved immunogenicity by adjuvants? A meta-analysis of randomized trials.
abstract: BACKGROUND
  Patients with chronic kidney disease typically show an impaired immune response to hepatitis B virus vaccine compared with healthy individuals. A variety of inherited or acquired factors have been implicated in this diminished response. Some authors suggested a benefit with adjuvantation to improve the immunogenicity of existing HBV vaccines.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of adjuvantation for hepatitis B virus vaccine in patients with chronic kidney disease.
  
  
  METHODS
  Only prospective, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird with heterogeneity and subgroups analyses. The primary end-point of interest was the seroprotection rate after HBV vaccination with recombinant vaccine plus adjuvants (study group) versus recombinant vaccine alone (control group).
  
  
  RESULTS
  We identified ten studies involving 1228 unique patients with chronic kidney disease. Pooling of study results did not show a significant increase in seroprotection rate among study (HBV recombinant vaccine plus adjuvants) versus control (HBV recombinant alone) patients; the pooled odds ratio of seroprotection rate was 1.47 (95% CI: 0.88; 2.46, NS). The pooled OR for seroresponse rate after HBV vaccine (adjuvanted recombinant vaccine versus recombinant vaccine alone) did not change in the subgroup of studies based on novel adjuvant systems (i.e., HBV-AS04 or HBV-AS02), the pooled OR was 2.22 (95% CI, 0.72; 6.78), NS. Q-test for heterogeneity being 10.819 (P=0.004).
  
  
  CONCLUSIONS
  Our meta-analysis showed that adjuvanted hepatitis B vaccine did not significantly improve the seroprotection rate in patients with renal insufficiency. These results do not support adjuvantation as an approach to increase the immunogenicity of existing recombinant vaccines towards HBV in this high-risk population.
authors.affiliation: Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Milano, Italy. fabrizi@policlinico.mi.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabrizi
authors.forename: Vivek
authors.initials: V
authors.lastname: Dixit
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000276:immunology*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic