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

Abstract

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.