Heplisav-B Vaccine Bests Standard 3-Dose Series in Heart, Lung Transplant Candidates

Chia-Yu Chiu, MD

Credit: University of Colorado

Findings from a recent study suggest Heplisav-B should be the preferred hepatitis B virus (HBV) vaccine in the pretransplant setting for thoracic organ transplant candidates, highlighting superior compliance and higher seroprotection rates than the conventional 3-dose series.¹

Study results additionally showed Heplisav-B was a significant independent predictor of achieving HBV seroprotection, although being ≥ 60 years of age and having pretransplant HBsAb level between 10 and 100 IU/L were identified as risk factors for HBV seroprotection loss following thoracic organ transplantation by 30 days posttransplantation.¹

“To the best of our knowledge, the current study is the largest to analyze HBV vaccine compliance, and it is the first study to report HBV vaccine seroprotective response for thoracic organ transplant candidates,” Chia-Yu Chiu, MD, an assistant professor of medicine at University of Colorado School of Medicine, and colleagues wrote.¹

Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation recommend HBV vaccination for all solid organ transplant candidates and assessment of hepatitis B surface antibody (HBsAb) levels 1-2 months after vaccine completion to determine pretransplant seroprotection. However, with different vaccines available to patients with varying surface antigen quantities and dosing strategies, understanding trends in HBsAb levels and how to optimize HBV vaccination protocols in this patient population is important but not well explored to date.^1,2

To evaluate compliance with HBV vaccination and differences in seroprotection rates among thoracic organ transplant candidates receiving different HBV vaccines, investigators conducted a retrospective study of adult heart and/or lung transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Patients were categorized into 3 groups at the time of pretransplant evaluation:

• HBV infected: HBsAg+ or anti-HBc+ (Group 1)
• HBV immune: Anti-HBc−, HBsAb ≥ 10 IU/L (Group 2)
• HBV non-immune: Anti-HBc−, HBsAb < 10 IU/L (Group 3)

Investigators noted HBV vaccination was not offered to patients in Group 1 and Group 2 per institutional protocol. Conventional recombinant hepatitis B vaccines (Recombivax HB 40 mcg/mL, 3-dose series at 0, 1, and 6 months) were used before 2020 and CpG-adjuvanted recombinant hepatitis B vaccine (Heplisav-B, 2-dose series at 0, 1 month) was used after 2020. Following pretransplant evaluation, patients received vaccines within Mayo Clinic institutions or from local providers.¹

Investigators collected hepatitis B surface antibody (HBsAb) ≥ 1 month after HBV vaccine completion and categorized results into 3 categories: HBsAb < 10 IU/L; HBsAb between 10 and 99 IU/L; and HBsAb > 100 IU/L. Loss of HBV seroprotection was defined as HBsAb < 10 IU/L at 30 days after transplantation, a time frame investigators chose because HBsAb was checked uniformly at this point in their institution.¹

During the study period, infectious disease consultants evaluated 1164 patients, 48 (4%) of whom had HBV infection (Group 1) and 194 (17%) of whom had seroprotection against HBV (Group 2). The remaining 922 patients were eligible for HBV vaccination, most of whom were male (69%), White (80%), heart transplant candidates (53%), and evaluated by infectious disease clinic at outpatient basis (79%).¹

Among the 922 patients eligible for HBV vaccination, 430 (47%) patients completed the HBV vaccine series pretransplant, 299 (32%) did not receive any HBV vaccine, and 193 (21%) patients did not complete the HBV vaccine series. Investigators pointed out patients who received Heplisav-B were more likely to complete the vaccine series than Recombivax HB (81% vs 60%; P <.001), as were patients who were evaluated for infectious diseases in outpatient settings (57% vs 5% in inpatient settings; P <.001).¹

Of 322 patients who had their HBsAb level checked ≥ 1 month after completing the HBV vaccine series, 224 achieved HBV seroprotection. Among this group, 163 (51%) patients completed Recombivax HB and 159 (49%) completed Heplisav-B. Investigators noted that compared with patients who completed Recombivax HB, patients who completed Heplisav-B had a higher rate of seroprotection (75% vs 64%; P = .023).¹

A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. In univariate analysis, female sex, non-obesity, no steroid exposure, and receiving Heplisav-B were significant factors linked to achieving HBV seroprotection. However, multivariate logistic regression analysis identified a single independent predictor for HBV seroprotection: receiving Heplisav-B (adjusted odds ratio [aOR], 1.723; 95% confidence interval [CI], 1.056–2.810; P .029).¹

On the day of transplantation, 69 (48%) patients had HBsAb levels ≥ 100 IU/L, while 76 (52%) had HBsAb levels between 10 and 100 IU/L. By 30 days after transplantation, investigators noted HBV seroprotection loss occurred in 38 (26%) recipients and was more frequent in patients with HBsAb between 10 and 100 IU/L at D0 than those with HBsAb ≥ 100 IU/L at D0 (46% vs 4%; P <.001). Multivariate logistic regression analysis identified age ≥ 60 years (aOR, 2.503; 95% CI, 1.026–6.107; P = .044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI, 5.211–66.209; P <.001) as predictors of HBV seroprotection loss at 30 days posttransplant.¹

Investigators outlined multiple limitations to these findings, including the retrospective study design with a standardized timeframe for checking HBsAb levels after vaccine completion; potential underestimation of vaccine compliance due to patients not reporting vaccination received from local providers; and the lack of consideration for the longevity of HBV seroprotection, as HBsAb levels were only measured 30 days after transplantation.¹

“Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav-B provided a higher vaccine completion rate and seroprotection than the 3-dose Recombivax HB,” investigators concluded.¹ “Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L.”

References

1. ^{Chiu CY, Sampathkumar P, Brumble LM, et al. Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients. Clinical Transplantation. https://doi.org/10.1111/ctr.15464}
2. ^{Malinis M, Boucher HW; AST Infectious Diseases Community of Practice. Screening of donor and candidate prior to solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. doi:10.1111/ctr.13548}