Efficacy and Safety of Reinforced Versus Standard Vaccine Schedule Towards Hepatitis B In Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Context The immunogenicity of the hepatitis B virus vaccine is reduced in patients with renal failure compared with the non-uraemic population. A variety of approaches have been suggested to improve the immune response in uraemic population including an increase in dose of the hepatitis B vaccine. Objective To compare the efficacy and safety of hepatitis B vaccine schedules based on greater versus standard doses of HB vaccine in patients with chronic kidney disease stages 3 - 5. Evidence Acquisition We carried out a systematic review of the medical literature with a meta-analysis of randomized trials comparing seroprotection rates after greater vs. standard doses of the HB vaccine. The odds ratio to obtain seroprotection among patients who received greater (study group) vs. standard (control group) doses was the end-point of interest. We used a random-effects approach, as described by DerSimonian and Laird, with heterogeneity and subgroup analyses. Results We retrieved 11 clinical trials (n = 870 unique patients); 2 (n = 141 patients) and 8 studies (n = 689) included CKD patients on pre-dialysis and dialysis stage, respectively. Three trials (n = 368 patients) employed plasma-derived vaccine; 8 (n = 502) adopted recombinant vaccine. Aggregation of study results (n = 10 studies) showed that the seroprotection rate (short-term follow-up) towards HB virus was higher among patients receiving greater than standard doses of vaccine [pooled OR, 2.10, 95% confidence intervals, 1.15 - 3.82]. The P-value was 0.0001 for our test to study heterogeneity. The seroprotection rate towards HBV was much greater in the subset of trials (n = 2) based on plasma-derived vaccine (OR, 3.78; 95% CI, 2.35; 6.07), and no heterogeneity was found (NS). In the subset of RCTs (n = 8 studies), the seroprotection rate was higher among patients receiving greater doses of vaccine towards HBV, OR, 2.01 (95% CI, 0.92; 4.39), with significant heterogeneity (P = 0.002). Tolerance was satisfactory and no dropouts due to side effects were reported. Conclusions Vaccine schedules based on greater than standard doses of HB vaccine offer higher immunogenicity in patients with chronic kidney disease. These results support the current recommendations to give higher doses of HBV vaccine to susceptible dialysis population in order to increase the sero-protection rate. Further research is needed to assess whether these findings apply to HB vaccines provided with novel adjuvants.