Vaccine-Induced Anti-HBs Response is Associated with Protection Against Hepatitis B Virus Reactivation after...

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with resolved HBV infection undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Although HBV DNA-guided preemptive nucleos(t)ide analog therapy prevents HBV-related hepatitis, strategies to prevent HBV reactivation itself remain limited. Hepatitis B vaccination after allo-HCT has been suggested as a potential preventive strategy, but prospective randomized evidence is lacking. To evaluate whether hepatitis B (HepB) vaccination reduces HBV reactivation after allo-HCT and to examine the association between vaccination-induced anti-hepatitis B surface antibody (anti-HBs) response and protection against HBV reactivation. In this multicenter randomized controlled trial (UMIN000034113), adults who were hepatitis B surface antigen-negative and anti-hepatitis B core antigen-positive and underwent first allo-HCT were prospectively enrolled. At 140 days post-HCT, patients without HBV reactivation were randomized to receive HepB vaccination or no vaccination. HBV DNA levels and anti-HBs titers were centrally monitored for 2 years after transplantation. The primary endpoint was HBV reactivation, defined as HBV DNA ≥ 1.3 log IU/mL. Vaccine response was defined as anti-HBs response, requiring both an increase in anti-HBs from baseline and a post-vaccination anti-HBs ≥ 10 mIU/mL. Among 109 enrolled patients, 64 were randomized. With a median HBV DNA follow-up of 19.4 months, HBV reactivation occurred in 6 of 33 patients in the vaccination group, including 2 who experienced reactivation before receiving the first vaccine dose, and 9 of 31 patients in the control group. Probabilities of HBV reactivation were 19.8% and 37.9% in the HepB vaccination and control groups, respectively, at 18 months after randomization (P = .205). Baseline anti-HBs <10 mIU/mL was a significant risk factor for HBV reactivation. No HBV-related hepatitis was observed. Vaccine responses were achieved in 9 of 29 patients after the initial series and in 5 of 10 after the additional series. Importantly, HBV reactivation did not occur after patients achieved anti-HBs response, although several reactivation events occurred before vaccination or before anti-HBs response was achieved. No severe vaccine-related adverse events were observed. Although HepB vaccination did not significantly reduce HBV reactivation, it was feasible and induced anti-HBs response in a subset of patients. Achieving vaccine-induced anti-HBs response may provide protective immunity against HBV reactivation after allo-HCT.