Immunized Against Hepatitis B Virus Allografted Recipients Are at High Risk for Gradual Surface Antibody (HbsAb) Disappearance Post Transplant, Regardless of Adoptive Immunity Transfer: A Study of 82 Allografted Long Term Survivors.
Authors: Kaloyannidis Panayotis , Yannaki Evangelia , Batsis Ioannis , Adamidou Despoina , Bartzoudis Demetrios , Papathanasiou Maria , Mallouri Despoina , Sakellari Ioanna , Fassas Athanasios , Anagnostopoulos Achilles 
Published: October 2019

Abstract
The presence of Hepatitis-B virus(HBV) surface antibody(HbsAb) is a strong indicator for the existence of HBV-immunity. Immunosuppressed allografted recipients are at risk of developing HBV hepatitis due to the potential loss of their immunity against HBV. The primary aim of the present study was to evaluate the incidence of HbsAb eradication post allo-transplantation, the potential risk factors and the impact of adoptive immunity transfer in the HbsAb loss. Additionally, to estimate the cumulative incidence of HBV infection in patients (pts) with HbsAb disappearance. Eighty-two immunized recipients aged 27(14–54) years and their donors were retrospectively studied. Fifty-six pts were naturally immunized while 26 were vaccinated. The median follow-up period was 36(6–132) months. Seventy-two were transplanted from siblings (4 with 1 Ag mismatch). Seven donors were matched unrelated volunteers, 2 were twins and 1 was haploidentical. Eighty-one pts received myeloablative conditioning. Marrow (BM) was infused in 23 pts, peripheral stem cells (PBSC) in 58 and BM plus PBSC in 1, with a median number of CD34:4,45x106/Kg, CD3:2,77x108/Kg, CD4:1,16x108/Kg, CD8: 1,06x108/Kg. Antithymocyte globulin (ATG) was administered to 15 and steroids to 54 pts. Thirty pts developed acute and 71 chronic graft versus host disease (cGVHD). Forty-six donors were non-immunized, 19 vaccinated and 13 naturally immunized. Data on immunity origin were missing for 4 donors. HbsAb disappearance was observed in 39/82 pts, 24(6–60) months post transplant with a probability of loss 90% at 5 years. Multivariate analysis revealed as significant risk factors for HbsAb loss the BM graft, ATG administration, age (<30years) and cGvHD development. The type of donor’s immunization had no significant impact, although the probability of losing HBV-immunity was 100%, 78%, and 58% for pts transplanted from nonimmunized, vaccinated and naturally immunized donors, respectively. As the adoptive transfer of HBV immunity is a well-documented phenomenon, we studied separately, in the 36 allografted pts from immunized donors, the potential risk factors for HbsAb loss. Multivariate analysis identified as risk factors for this loss, the use of ATG, BM graft, and donor’s vaccination. The use of steroids had a strong tendency towards significance(p:0,06). Among the 39 pts who lost immunity, 6 developed hepatitisB. All had a previous natural immunity. Four had been transplanted from non-immunized and 2 from naturally immunized donors and all had been treated or were on intensive therapy for refractory cGvHD. The probability for HBV infection for pts who lost the HbsAb, regardless of immunity origin, was 18% at 12 years. Six of 28 naturally immunized pts who lost the HbsAb developed hepatitis. In this cohort of pts the probability of HBV reactivation was estimated to be 26% at 12 years. In our study, the majority of pts lost their pre-transplant protection against HBV while the adoptive transfer of immunity, although established, didn’t offer long-lasting protection. As the possibility of hepatitisB is not negligible, serial serological monitoring and timely vaccination schedule for re-immunization in the early but also in the late post transplant period, might be necessary for patients with low or decreasing HbsAb titers.