Hepatitis B seropositivity is associated with increased cardiac allograft vasculopathy after heart transplantation

Background: Viral triggers have been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), the Achilles heel of heart transplantation (HT). Cytomegalovirus is associated with impaired coronary endothelial function, and in pediatric HT patients a variety of viruses, particularly adenovirus, are associated with graft dysfunction or loss. Hepatitis B virus (HBV) is associated with vasculitis and vascular processes in non-HT patients. We thus investigated the association between HBV seropositivity and CAV after HT.

Methods: The 173 HT patients assessed for HBV serology from 1997 to 2017 were divided into hepatitis B core antibody (HBcAb) positive (n=29) and HBcAb negative (n=144) groups. Primary outcomes were CAV and the combined end-point of CAV or cardiovascular mortality.

Results: Baseline patient and donor clinical and demographic data for the 2 groups were similar. Kaplan-Meier analysis showed that 20-year freedom from CAV was significantly higher in the HBcAb-negative vs HBcAb-positive group (80 vs 50%, log-rank p=0.003, Figure 1A). Similarly, 20-year freedom from CAV or cardiovascular mortality was higher for the HBcAb-negative group (75 vs 45%, log-rank p=0.018). Consistently, multivariable analysis showed HBcAb positivity to be independently associated with a significant ⁓3-fold increased risk of CAV (95% CI 1.38-5.01, p=0.003, Figure 1B), and a 2-fold increased risk of CAV or cardiovascular mortality (95% CI 1.11-3.90, p=0.021).

Conclusion: Hepatitis B seropositivity is independently associated with an increased risk of CAV in HT recipients. Future studies are needed to examine the effect of anti-viral therapies.