Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate in Lowering the Risk of HCC Development in Patients With CHB

BACKGROUND: Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are guideline-endorsed first-line options for antiviral-naive chronic hepatitis B (CHB). We compared their associations with hepatocellular carcinoma (HCC) occurrence. METHODS: We assembled a multicenter cohort of 1364 treatment-naive CHB patients initiating either TAF (n = 322) or TDF (n = 1042) between 2012 and 2019. Confounding was addressed using 1:2 propensity score (PS) matching and inverse probability of treatment weighting (IPTW). RESULTS: The PS-matched analytic set comprised 966 patients (TAF 322; TDF 644). Over 60 months, nine HCC events occurred (two TAF and seven TDF events). Crude incidence rates were 0.17 and 0.27 per 100 person-years for TAF and TDF, respectively. Five-year cumulative risks were 0.6% (TAF) versus 1.0% (TDF). In multivariable models, TAF remained protective (adjusted hazard ratio [aHR]: 0.29, 95% confidence interval [CI]: 0.13-0.66; p < 0.01). Findings were directionally consistent across subgroups, with the strongest associations observed among patients without diabetes, those who were hepatitis B e antigen-positive, and those with baseline HBV DNA in the 5-8 log10 IU/mL range. In IPTW analyses, TAF was likewise associated with lower HCC risk (aHR: 0.31, 95% CI: 0.14-0.68; p < 0.01). CONCLUSIONS: Compared with TDF, TAF use was associated with an approximately 71% reduction in HCC hazard. Larger cohorts with longer follow-up are warranted to corroborate these observations.