Comparing Hepatitis B Vaccination Schedules in Patients on Hemodialysis (3v4-HEP-DOSE)

Hepatitis B virus (HBV) infection remains a significant concern in hemodialysis units due to repeated vascular access, blood exposure, and the shared dialysis environment. While routine screening, infection control practices, and vaccination programs have reduced HBV transmission in dialysis settings, patients with end-stage renal disease (ESRD) mount a markedly blunted immune response to hepatitis B vaccination compared to the general population. Whereas over 90% of healthy individuals achieve protective antibody levels after standard vaccination, only 50-85% of dialysis patients reach seroprotection, even when higher vaccine doses are used. This immune hyporesponsiveness has been attributed to uremia-associated defects in antigen presentation, T-cell function, and B-cell antibody production.

Several strategies have been investigated to improve seroconversion rates in this population, including increased antigen dose, additional booster doses, intradermal administration, and adjuvanted vaccines. Among these, modifying the number of doses in the immunization schedule (commonly 3-dose vs. 4-dose regimens) has shown inconsistent results across studies. Some trials report significantly higher seroprotection with a 4-dose schedule compared to 3 doses, while others report no statistically significant difference between the two approaches. This inconsistency, combined with a lack of locally generated data from Pakistani dialysis populations, has created uncertainty for clinicians in selecting the optimal immunization strategy for hemodialysis patients.

This randomized controlled trial is designed to directly compare a 3-dose and a 4-dose schedule of double-dose (40 mcg) recombinant hepatitis B vaccine administered intramuscularly to patients undergoing maintenance hemodialysis. Randomization will be performed using the lottery method to allocate eligible participants into one of the two vaccination groups. Both groups will receive the same 40 mcg antigen dose per injection; the schedules differ only in timing and number of doses (0, 1, and 6 months for the 3-dose group vs. 0, 1, 2, and 6 months for the 4-dose group).

At baseline, demographic and clinical data will be collected, including age, gender, body mass index, and duration on maintenance hemodialysis, along with relevant comorbidities (diabetes mellitus, hypertension, and ischemic heart disease), as these factors are known to influence vaccine immunogenicity in dialysis populations. Anti-HBs antibody titers will be measured 30 days after completion of the assigned vaccination schedule using a quantitative chemiluminescence immunoassay. Seroprotection will be defined as an Anti-HBs titer ≥10 mIU/mL. Participants who do not achieve this threshold will be offered an additional vaccine dose as part of routine clinical care.

Post-hoc stratified analysis will be performed by age, gender, BMI, and duration on hemodialysis to evaluate whether these variables modify the relationship between vaccination schedule and seroprotection. Findings from this trial are intended to generate the first local evidence from a Pakistani dialysis cohort on the comparative efficacy of these two immunization schedules, with the aim of informing more effective, evidence-based hepatitis B vaccination protocols in hemodialysis units.