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

Sci Rep. 2025 Feb 15;15(1):5637. doi: 10.1038/s41598-025-89325-1.

Abstract

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.

Keywords: Besifovir divipoxil maleate; Health; Hepatocellular carcinoma; Insurance; Prognosis.

Publication types

  • Comparative Study

MeSH terms

  • Adenine* / adverse effects
  • Adenine* / analogs & derivatives
  • Adenine* / therapeutic use
  • Adult
  • Aged
  • Alanine
  • Antiviral Agents* / adverse effects
  • Antiviral Agents* / therapeutic use
  • Carcinoma, Hepatocellular* / chemically induced
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / etiology
  • Female
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Incidence
  • Liver Neoplasms* / chemically induced
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / etiology
  • Male
  • Middle Aged
  • Republic of Korea / epidemiology
  • Risk Factors
  • Tenofovir* / adverse effects
  • Tenofovir* / analogs & derivatives
  • Tenofovir* / therapeutic use

Substances

  • Tenofovir
  • Antiviral Agents
  • Adenine
  • tenofovir alafenamide
  • Alanine