Comparing Hepatitis B Vaccination Schedules in Patients on Hemodialysis

Hepatitis B virus (HBV) infection remains a significant concern in hemodialysis units dueto repeated vascular access, blood exposure, and the shared dialysis environment. Whileroutine screening, infection control practices, and vaccination programs have reduced HBVtransmission in dialysis settings, patients with end‐stage renal disease (ESRD) mount amarkedly blunted immune response to hepatitis B vaccination compared to the generalpopulation. Whereas over 90% of healthy individuals achieve protective antibody levelsafter standard vaccination, only 50‐85% of dialysis patients reach seroprotection, evenwhen higher vaccine doses are used. This immune hyporesponsiveness has been attributed touremia‐associated defects in antigen presentation, T‐cell function, and B‐cell antibodyproduction.Several strategies have been investigated to improve seroconversion rates in thispopulation, including increased antigen dose, additional booster doses, intradermaladministration, and adjuvanted vaccines. Among these, modifying the number of doses inthe immunization schedule (commonly 3‐dose vs. 4‐dose regimens) has shown inconsistentresults across studies. Some trials report significantly higher seroprotection with a4‐dose schedule compared to 3 doses, while others report no statistically significantdifference between the two approaches. This inconsistency, combined with a lack oflocally generated data from Pakistani dialysis populations, has created uncertainty forclinicians in selecting the optimal immunization strategy for hemodialysis patients.This randomized controlled trial is designed to directly compare a 3‐dose and a 4‐doseschedule of double‐dose (40 mcg) recombinant hepatitis B vaccine administeredintramuscularly to patients undergoing maintenance hemodialysis. Randomization will beperformed using the lottery method to allocate eligible participants into one of the twovaccination 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 the3‐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, bodymass index, and duration on maintenance hemodialysis, along with relevant comorbidities(diabetes mellitus, hypertension, and ischemic heart disease), as these factors are knownto influence vaccine immunogenicity in dialysis populations. Anti‐HBs antibody titerswill be measured 30 days after completion of the assigned vaccination schedule using aquantitative chemiluminescence immunoassay. Seroprotection will be defined as an Anti‐HBstiter ≥10 mIU/mL. Participants who do not achieve this threshold will be offered anadditional vaccine dose as part of routine clinical care.Post‐hoc stratified analysis will be performed by age, gender, BMI, and duration onhemodialysis to evaluate whether these variables modify the relationship betweenvaccination schedule and seroprotection. Findings from this trial are intended togenerate the first local evidence from a Pakistani dialysis cohort on the comparativeefficacy of these two immunization schedules, with the aim of informing more effective,evidence‐based hepatitis B vaccination protocols in hemodialysis units.