Meta-analysis: the effect of age on immunological response to hepatitis B vaccine in end-stage renal disease


Dr F. Fabrizi, Divisione di Nefrologia, Dialisi e Trapianto, Ospedale Maggiore, IRCCS, Pad. Croff, via Commenda, 15 Milano, 20122 Italy.


Background : Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non-uraemic population. A variety of inherited or acquired factors have been implicated in this diminished response. Age-associated changes in immune status may contribute to decreased vaccine efficacy in older individuals although contradictory results have been reported in individuals with normal kidney function.

Aims : To evaluate the relationship between age and immune response to hepatitis B vaccine in patients with end-stage renal disease by performing a systematic review of the literature with a meta-analysis of clinical trials.

Method : We used the random effects model of DerSimonian and Laird; sources of heterogeneity in effect estimates were explored by performing sensitivity analyses.

Results : We identified 17 clinical trials (1800 unique patients); six (35%) were controlled studies. Pooling of study results demonstrated a significantly decreased risk of response to hepatitis B vaccine among older dialysis patients (overall risk ratio: 0.74; 95% confidence intervals: 0.70–0.79). The P-value was 0.0139 for our test of study heterogeneity. A lowered risk of response to hepatitis B vaccine persisted after exclusion of trials based on plasma-derived vaccines; it was present even when ‘older’ individuals were defined as being as 50 years (RR: 0.85, 95% CI: 0.75–0.96) or more (cut-off 60 years RR: 0.75; 95% CI: 0.66–0.85). An effect of age on seroprotection rate was present in all clinical reports, irrespective of the geographic origin of the study group: Europe (RR: 0.76; 95% CI: 0.70–0.83) North America (RR: 0.67; 95% CI: 0.60–0.74) or other countries (RR: 0.83; 95% CI: 0.71–0.97). Additional doses of vaccine did not appear to have an impact on RR of response by age.

Conclusions : Our meta-analysis showed a clear association between older age and impaired response to hepatitis B virus vaccine in end-stage renal disease patients. Such a relationship is biologically plausible. Vaccination schedules with adapted vaccine doses and frequent serum testing for loss of immunity against hepatitis B virus are recommended in elderly patients on maintenance dialysis.