Hepatitis B Virus Vaccination after Allogeneic Hematopoietic Cell Transplantation Prevents Post-Transplantation Hepatitis B Virus Reactivation

Abstract

Hepatitis B virus (HBV) reactivation in allogeneic hematopoietic cell transplantation (HCT) recipients with evidence of pretransplantation resolved HBV infection is an important cause of morbidity, usually occurring 1 year or later after HCT. We retrospectively studied a cohort of allogeneic HCT recipients with resolved HBV infection, some of whom were vaccinated for HBV following transplantation, to understand whether post-HCT HBV vaccination influenced the risk of HBV reactivation. The study included all patients with resolved HBV who underwent allogeneic HCT at our institution between January 1, 2000, and December 31, 2015, where HBV vaccination starting at 1 year after HCT became standard in 2012 and antiviral prophylaxis is not used. Resolved HBV infection was defined as positive HBV-core IgG (HBcAb), negative HBV-surface antigen (HBsAg), and undetectable HBV DNA before HCT. HBV reactivation was defined as the development of detectable HBsAg and HBV DNA after HCT. Follow-up for outcomes concluded on January 1, 2018. Among 136 patients with resolved HBV infection before HCT, 19 developed reactivation during follow-up (cumulative incidence, 14%). The median time to HBV reactivation was 21 months (range, 2 to 47 months). When accounting for competing risks, the cumulative incidence of HBV reactivation among HCT recipients who survived for 1 year or longer after transplantation without early HBV reactivation and were HBV vaccinated versus those who were unvaccinated was 2.9% versus 10.0% at 2 years post-HCT and 6.6% versus 26.5% at 4 years post-HCT (P=0.03, Gray's test). In a time-dependent Cox model, the adjusted hazard ratio (aHR) of HBV reactivation in patients with a pretransplantation HBsAb level >10 IU/L was 0.34 (95% confidence interval [CI], 0.13 -0.90). The aHR of HBV reactivation in patients who were vaccinated with 2 or more doses of recombinant HBV vaccine after HCT was 0.18 (95% CI, 0.04-0.80) compared with those who received 1 or no post-HCT vaccine doses. HBV reactivation is a late complication of allogeneic HCT in at-risk recipients, particularly in those with low pre-HCT HBsAb. HBV vaccination starting at 1 year after HCT may be protective.