CHRONIC hepatitis B (CHB) remains a leading cause of hepatocellular carcinoma (HCC), particularly in endemic regions, where more than half of cases are linked to persistent infection. The risk arises through both direct mechanisms, such as viral DNA integration and oncogenic protein expression, and indirect mechanisms including chronic inflammation, fibrosis, and cirrhosis. Suppressing viral replication with antiviral therapy (AVT) is therefore central to reducing liver damage and cancer risk.
Established first-line therapies include entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). While these agents effectively control viral replication, they cannot eradicate hepatitis B virus (HBV), and some are associated with adverse renal or bone effects. Besifovir dipivoxil maleate (BSV), a newer oral nucleotide analogue approved in South Korea in 2017, has demonstrated comparable antiviral efficacy with a lower incidence of such side effects. It is recommended as first-line therapy in Korean guidelines, yet evidence regarding its impact on HCC development has been limited.
This multicentre retrospective study evaluated the long-term risk of HCC in treatment-naïve CHB patients receiving BSV compared to those treated with ETV, TDF, or TAF. In a large cohort of 2,889 patients, BSV use was associated with a similar or significantly lower risk of HCC development. The findings remained robust across weighted and propensity-matched analyses, and subgroup analyses accounting for fibrosis confirmed the benefit, particularly compared to ETV.
Potential mechanisms behind BSV’s protective effect may mirror those described for tenofovir-based therapies, such as modulation of inflammatory and oncogenic pathways. An additional factor may be routine L-carnitine supplementation, required with BSV to offset drug-induced depletion, which itself has been linked to reduced hepatocarcinogenesis in experimental models.
While the follow-up period was relatively short and BSV remains largely confined to South Korea, this study provides the first direct comparative evidence of its role in lowering HCC risk.
In conclusion, BSV demonstrated non-inferior, and in some analyses superior, efficacy compared with established agents in reducing liver cancer development among CHB patients. Longer-term studies and broader availability will be crucial to validate and expand these findings.
Reference
Lee JS et al. Besifovir dipivoxil maleate versus other antivirals in reducing hepatocellular carcinoma in chronic hepatitis B. Sci Rep. 2025;15(1):31879.
