Antiviral Therapy and Post‐Resection Outcomes in Patients With Hepatitis B Virus‐Related Hepatocellular Carcinoma

Background & Aims The comparative outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) in patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) after curative resection remain unclear. This study aimed to evaluate the survival benefits of these antiviral regimens in a large real‐world cohort. Methods We analysed 902 patients with BCLC stage 0 or A HBV‐related HCC who underwent curative resection between September 2001 and August 2025. Patients received ETV ( n = 474), TDF ( n = 363), or TAF ( n = 65) as first‐line therapy within 3 months post‐resection. Inverse probability of treatment weighting (IPTW) was implemented to balance baseline covariates. The primary and secondary endpoints were overall survival (OS) and recurrence‐free survival (RFS). Results The IPTW‐adjusted 5‐year OS rates for ETV, TDF, and TAF were 90.7%, 95.2%, and 97.1%, respectively (global p = 0.079). The 5‐year RFS rates were comparable for ETV, TDF, and TAF (57.4% vs. 61.0% vs. 69.4%; global p = 0.533). In multivariable Cox regression analysis, however, TDF was independently associated with a significantly lower risk of death compared with ETV (aHR 0.48; 95% CI, 0.26–0.89; p = 0.021). TAF showed higher survival rates compared to ETV, although the difference did not reach statistical significance (aHR 0.34; 95% CI, 0.04–2.55; p = 0.292). Conclusion The choice of antiviral regimen was not associated with RFS after curative resection for HBV‐related HCC, whereas TDF was independently associated with improved OS compared with ETV. Further large‐scale studies are warranted to validate the long‐term prognostic impact of TAF.