Comparison of hepatocellular carcinoma incidence after long-term treatment with besifovir vs. tenofovir AF

Besifovir dipivoxil maleate (BSV) is a novel antiviral agent widely used in South Korea for treating chronic hepatitis B (CHB). This study aimed to compare the incidence of hepatocellular carcinoma (HCC) following long-term use of BSV versus tenofovir alafenamide fumarate (TAF), utilizing large-scale national data. A total of 41,949 patients were analyzed, with propensity score matching (PSM) yielding 2,239 BSV and 6,717 TAF patients. The HCC incidence rate per 1,000 person-years was 1.8 for BSV versus 2.4 for TAF before matching (P = 0.057) and 1.6 versus 2.2 after matching (P = 0.284). Multivariate Cox regression identified age, male sex, antiviral duration, Charlson Comorbidity Index (CCI) score, and decompensated cirrhosis as significant risk factors for HCC, while antiviral type was not (HR 1.12, P = 0.413). Subgroup analyses showed no significant differences in HCC incidence between BSV and TAF in cirrhotic or non-cirrhotic patients. These findings suggest that BSV offers comparable efficacy to TAF in preventing HCC and is a promising option for CHB management. Longer-term studies with larger cohorts are necessary to confirm these results and assess the full impact of BSV on HCC prevention.