Hepatitis B Reverse Seroconversion in Long Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Le Quan , Savani Bipin N. , Shenoy Aarthi , Kozanas Eleftheria , Barrett A. John 
Published: April 2020

Abstract
Reverse seroconversion (RS) known as reactivation of resolved hepatitis B virus (HBV) infection is a complication after allogeneic hematopoietic stem cell transplantation (SCT) in patients exposed to hepatitis B virus. Four hundred thirty six (436) patients with hematological disorder received SCT from an HLA identical sibling in our institute between September 1993 and June 2004. Of these, 103 patients who are 3 or more years post-transplantation have been enrolled in a long-term evaluation protocol. Sixteen had pre-transplant resolved HBV infection (negative HBsAg, positive anti-HBs and anti-HBc antibodies). We investigated the serologic markers of HBV infection in this cohort (median follow-up 59.5 months, range 40–113). Diagnoses included chronic or acute myelogenous leukemia and myelodysplastic syndrome (14), acute lymphoblastic leukemia (1), and severe aplastic anemia (1). Median age at SCT was 32 years (range 10–56). Thirteen patients were positive for anti-HBc and anti-HBs. One had anti-HBc, one had anti-HBs alone, and 1 had no antibodies to hepatitis B. None had detectible HBsAg (HBV surface antigen) at transplant. Twelve patients (median age 39.5 years) received a 12–13.6 Gy total body irradiation (TBI)-based myeloablative SCT followed by a T-cell depleted peripheral blood stem cell transplantation (PBSCT). Four patients (median age 31 years) received a reduced-intensity regimen of fludarabine 125 mg/m2 and cyclophosphamide 60 mg/kg, followed by a PBSCT. All received cyclosporine as graft-verse-host disease (GVHD) prophylaxis. Nine developed acute GVHD, and 13 developed chronic GVHD. Nine (56%) patients received immunosuppressive therapy (IST) for chronic GVHD beyond 3 years from SCT. Fifteen (94%) patients were alive with a median follow-up of 59.5 months. One patient with RS of HBV died at 59 months after SCT. Six (38%) patients developed RS of hepatitis B with reappearance of HBsAg, 21–101 (median 29.5) months after SCT. Four (67%) of the 6 developed clinical hepatitis and received Lamivudine treatment with a decrease of HBV viral load. There was no significant difference in median age of 6 patients with, and 10 patients without RS (38 vs 32 years). RS of hepatitis B was associated with prolonged immunosuppressive therapy for cGVHD. Theses results show that RS of HBV post SCT is a significant long-term complication of patients with pre-transplant resolved HBV infection. This emphasizes the importance of long-term hepatitis B serologic monitoring, post-transplant prophylaxis with Lamivudine, HBV vaccine, and prompt initiation of Lamivudine treatment if RS of HBV occurs.
Variable With RS of HBV Without RS of HBV Cases 6 (38%) 10 (62%) Age in years (median, range) 38 (10–46) 32(13–56) Myeloablative 4 8 Reduced intensity 2 2 aGVHD 2/6 (33%) 7/10 (70%) cGVHD 5/6 (83%) 8/10 (80%) IST for cGVHD &gt;3 years 4/6 (67%) 5/10 (50%) Lamivudine Treatment 4/6 (67%) Lamivudine Prophylaxis 5/10 (50%) HBV Vaccine after HSCT 5/10 (50%) RS of HBV in months (median, range) 29.5 (21–101) Follow-up in months (median, range) 71(55–107) 57.5 (40–113)