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

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.

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).

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).

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.