A Novel Strategy for the Prevention of Hepatitis B Virus-Related Hepatitis Following Allogeneic Hematopoietic Stem Cell Transplantation from Hepatitis B Surface Antigen-Positive Donors

Abstract

Hematopoietic stem cell transplantation (HSCT) is increasingly being applied globally. Cases in which healthy HSCT donors are chronically infected with hepatitis B virus (HBV) are relatively common in areas where HBV is endemic. Recipients of stem cells from such hepatitis B surface antigen (HBsAg)-positive donors are at risk of viral infection, and thus may develop HBV-related hepatitis. Given the lack of standardized approach to minimizing the risk of such infections from HBsAg+ donors during HSCT, we conducted this study with the aim of developing an efficient strategy to address this challenge. A strategy comprising antiviral treatment for detectable HBV-DNA in HBsAg+ donors, hepatitis B immune globulin (HBIG) administration in HBsAg- recipients with passive immunity, and prophylactic antiviral treatment for HBsAg+ recipients was developed. The strategy was validated using a case-control study of 40 recipients who received stem cells from HBsAg+ donors (group A) and 40 pair-matched controls who received stem cells from HBsAg- donors (group B). The cumulative incidence of HBV-related hepatitis was relatively similar in the 2 groups (group A: 8.5%; 95% confidence interval [CI], -.9% to 17.9%; group B: 7.9%; 95% CI, -.9% to 16.7%; P=.939). In HBsAg- recipients who received passive immunity from HBIG treatment, a significant negative linear correlation was observed between HBsAb titer in vivo and time in the first year after allo-HSCT (R2=.23; P < .001). This method was cost-effective, with a median cost of all HBV management of USD 332.1 (range, 172.7 to 1985.3), compared with USD 1464.9 (range 409.9 to 1985.3) for conventional strategies (P < .001). The novel strategy presented in here is robust in preventing HBV-related hepatitis after allo-HSCT with stem cells from HBsAg+ donors. This is important for the effective application of allo-HSCT in HBV-endemic areas without precluding the use of HBsAg+ donors.