Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Treated With Tenofovir Alafenamide or Tenofovir Disoproxil Fumarate

Background and Aims In phase 3 trials, tenofovir alafenamide (TAF) showed antiviral efficacy comparable to that of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB), with an improved safety profile. This study aimed to compare the clinical efficacy of TAF and TDF in terms of the risk of hepatocellular carcinoma (HCC). Methods We conducted a nationwide historical population cohort study on treatment‐naïve adult patients with CHB receiving TAF ( n = 29 309) or TDF ( n = 58 046) as first‐line therapy from 2017 to 2022 using data from the Korean National Health Insurance Service database. Cumulative HCC incidence and associated risk factors were estimated using competing risk factors. Propensity score (PS)‐matched analysis was used to minimise the confounding effects. Results A total of 54 185 patients were included in the study, with 20 994 in the TAF group and 33 191 in the TDF group. The annual incidence of HCC was significantly lower in the TAF group (7.5/1000 patient‐years [PYs]) than in the TDF group (10.3/1000 PYs; subdistribution hazard ratio [SHR], 0.74; p < 0.001). After PS matching, TAF continued to exhibit a protective effect against HCC (7.5/1000 PYs vs. 9.9/1000 PYs; p < 0.001). Multivariable analysis with Fine–Gray proportional subdistribution hazards model identified TAF as significantly associated with a reduced HCC incidence (SHR: 0.76; p < 0.001). Subgroup analysis confirmed the hepatoprotective effect of TAF against HCC even in patients with cirrhosis (SHR: 0.78; p = 0.003). Conclusion This study showed that TAF had a hepatoprotective effect against HCC in patients with CHB, providing valuable guidance for clinicians in selecting the appropriate initial treatment for these patients.