Entecavir versus tenofovir on recurrence of hepatitis B virus–related hepatocellular carcinoma in liver transplantation

Abstract

Abstract Background Considerable controversy exists regarding the superiority of tenofovir disoproxil fumarate (TDF) over entecavir (ETV) for reducing the risk of hepatocellular carcinoma (HCC). This study aimed to compare outcomes of ETV versus TDF after liver transplantation (LT) in patients with hepatitis B virus (HBV)-related HCC. Methods We performed a multicenter observational study using data from the Korean Organ Transplantation Registry. A total of 845 patients who underwent LT for HBV-related HCC were divided into two groups according to oral nucleos(t)ide analogue used for HBV prophylaxis post-LT: ETV group (n = 393) and TDF group (n = 452). HCC recurrence and overall death were compared in naïve and propensity score (PS)-weighted populations, and the likelihood of these outcomes according to the use of ETV or TDF were analyzed with various Cox models. Results At 1, 3, and 5 years, the ETV and TDF groups had similar HCC recurrence-free survival (90.7%, 85.6%, and 84.1% vs. 90.9%, 84.6%, and 84.2%, respectively, P = 0.982) and overall survival (98.4%, 94.7%, and 93.5% vs. 99.3%, 95.8%, and 94.9%, respectively, P = 0.480). The PS-weighted population showed similar results. In Cox models involving covariates adjustment, PS-weighting, competing risk regression, and time-dependent covariates adjustment, both groups showed a similar risk of HCC recurrence and overall death. In subgroup analyses stratified according to HCC burden (Milan criteria, Up-to-7 criteria, French alpha-fetoprotein risk score), pretransplantation locoregional therapy, and salvage LT, neither ETV nor TDF was superior. Conclusion ETV and TDF showed mutual non-inferiority for HCC outcomes when used for HBV prophylaxis after LT.