Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study

Abstract

Background: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. Materials and Methods: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. Results: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). Conclusion: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.