Post-transplant HBV reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-center retrospective cohort study in China

Background: Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. Methods: The study retrospectively analyzed HCC patients undergoing liver transplantation in two centers between January 2015 and December 2020. We reviewed post-transplant HBV status and its association with outcomes. Results: The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance (n=58) was poorer than those with HBsAg persistent negative (n=351) and positive (n=53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or > 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or > 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs 62.3%; P <0.01, and 16.4% vs 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (AUROC=0.78, C-index =0.73). Conclusions: Recipients with HBV reactivation had worse outcomes and higher tumor recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.