Erythropoietin Use and Immunogenicity of Hepatitis B Virus Vaccine in Chronic Kidney Disease Patients: A Meta-Analysis

Background: It is known that the immunogenicity of hepatitis B virus (HBV) vaccine is lower in uremic patients than healthy subjects. Numerous inherited or acquired factors have been implicated in this lowered response, and the high frequency of recombinant human erythropoietin use among patients on maintenance dialysis has been suggested to play a pivotal role. However, the impact of therapy with recombinant erythropoietin on the immune response to HBV vaccine in patients with chronic kidney disease (CKD) is not appropriately detailed. Aim: To evaluate the influence of human recombinant erythropoietin therapy on the immunological response to HBV vaccine in CKD patients by performing a systematic review of the literature with a meta-analysis of clinical studies. Methods: We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titers at completion of a hepatitis B vaccine schedule among human erythropoietin users versus those who did not receive the drug in a CKD population. Results: We identified 11 studies involving 862 unique patients with CKD. Aggregation of study results did not show a significant increase in response rates among erythropoietin user versus non-user patients (pooled odds ratio = 1.431; 95% CI 0.954; 2.146), according to a random-effects model. No heterogeneity was found, the p value was 0.1 for our test of study heterogeneity (Q = 14.147). Stratified analysis in various subgroups of interest did not significantly change these findings. Conclusions: Our meta-analysis showed no link between immunological response to HBV vaccine and therapy with human recombinant erythropoietin among individuals on long-term dialysis. We suggest the use of recombinant vaccine towards hepatitis B in patients on regular dialysis irrespective of erythropoietin treatment.