Antibodies to Hepatitis B Surface Antigen (HBsAb) Are Acquired after Allogeneic Stem Cell Transplantation in Non-B Hepatitis Virus-Infected Patients but Disappear over Time
Authors: Ren Jinhua , Xiao Tingting , Weng Yingxi , Zheng Rong , Zhang Yu , Xu Jingjing , Luo Xiaofeng , Zheng Zhihong , Chen Zhizhe , Hu Jianda , Yang Ting 
Published: February 2021

BACKGROUND:
There is currently no unified standard protocol for the prevention of hepatitis B virus (HBV) infection in patients with hematopoietic stem cell transplantation. The incidence of HBV infection is high in China, particularly in the Fujian Province of China. Nevertheless, there are also many transplanted patients who are not infected with HBV as indicated by serology markers (negative for HBsAg, anti-HBsAb, HBeAg, anti-HBeAb, anti-HBcAb, HBV-DNA). Therefore, there is a need to develop a protocol to prevent hepatitis virus infection in these non-infected patients.
AIMS:
This study aims to determine the changes in HBV immune status after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients not infected with HBV for establishing a management protocol to prevent HBV infection in these patients after allo-HSCT.
METHODS:
The study included 54 patients in non-B hepatitis virus-infected who received allo-HSCT at the Fujian Medical University Union Hospital between March 2013 and April 2020 for acute myeloid leukemia (n=22), acute lymphoblastic leukemia (n=18), chronic myeloid leukemia (n=3), aplastic anemia (n=5), lymphoma (n=2) and myelodysplastic syndrome (n=4). All patients were tested for hepatitis B serum markers by ELISA and HBV-DNA by PCR before and every 2 weeks after transplantation but did not receive hepatitis B immunoglobulin to prevent HBV infection. Four patients received Entecavir prophylactic antiviral therapy because the stem cells came from HBsAg positive donors (2 HBV-DNA negative, 2 HBV-DNA positive). Of the 50 HBsAg negative donors, 15 were anti-HBsAb negative, including 8 anti-HBcAb positive and 7 anti-HBcAb negative, and 35 were anti-HBsAb positive, of which 23 were anti-HBcAb positive and 12 anti-HBcAb negative.
RESULTS:
All 54 patients had changes in HBV immune status after allo-HSCT, including 48 cases positive for anti-HBsAb/anti-HBcAb (87.03%) and 7 cases positive for anti-HBsAb and negative for anti-HBcAb (12.96%). It means that all of these patients obtained protective antibodies against HBV. The median time (range) for HBV immune status changes was 5 (1-84) days after transplantation. The titer of HBsAb changed with immune reconstruction after transplantation. The median titers (mIU/ml) of HBsAb at Day 30, 60, 90, 120, 180 and 240 after transplantation were 258.49, 133.4, 33.17, 15.95, 26.89, and 27.99, respectively. On Day 30, 60, 90, 120, 180 and 240 post-transplantation, 18.91% (7/37), 41.17% (14/34), 50% (14/28), 72.2%, (13/18) of the anti-HBsAb and anti-HBcAb positive patients became negative. It means that these patients lost HbsAb but no new hepatitis B virus infection occurred during the median (range) follow-up of 299 (22-2572) days.
CONCLUSIONS:
After allo-HSCT, HBV-negative patients acquired HB surface antibodies, and the HBsAb titer gradually decreased to eventually disappear at the end of follow-up. Therefore, we do not recommend prophylactic anti-hepatitis B virus therapy in the early stage of hematopoietic stem cell transplantation in non-HBV infected patients.

Disclosures
No relevant conflicts of interest to declare.