Comparative Renal Safety of Besifovir Dipivoxil Maleate and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients: Insights From a Nationwide Cohort Study.

BACKGROUND: Besifovir dipivoxil maleate (BSV) is a novel antiviral agent approved in Korea for chronic hepatitis B (CHB) treatment. While previous comparative studies between BSV and tenofovir disoproxil fumarate (TDF) have suggested lower renal toxicity in BSV, these findings were limited by small sample sizes. This study aimed to comprehensively assess the incidence of chronic kidney disease (CKD) in CHB patients treated with BSV versus TDF using a nationwide cohort. METHODS: In this retrospective cohort study, we analyzed treatment-naïve CHB patients who initiated BSV or TDF therapy between January 2018 and December 2022. Using the South Korean national health database, we created balanced cohorts of 19,959 patients in the BSV group and 19,991 patients in the TDF group through inverse probability of treatment weighting (IPTW). The primary outcome was determined by CKD incidence. RESULTS: The incidence rate (IR) of CKD was lower in the BSV group than in the TDF group (2.29 vs. 3.42 per 1,000 person-years; incidence rate ratio [IRR], 1.50; 95% confidence interval [CI], 1.18-1.89; P < 0.001). Using BSV as the reference, the adjusted hazard ratio (HR) for CKD in the TDF group was 1.36 (95% CI, 1.07-1.73; P = 0.012). In patients aged 60 years and older, the difference in CKD incidence and risk between the 2 groups was more pronounced than in patients under 60 (IR, 4.47 vs. 7.52 per 1,000 person-years; IRR, 1.68; 95% CI, 1.10-2.57; P = 0.017 and HR, 1.62; 95% CI, 1.04-2.51; P = 0.032). CONCLUSION: BSV is linked to a lower incidence of CKD than TDF, particularly in patients aged 60 and older, suggesting BSV may be a safer treatment option in elderly patients at high risk of renal impairment.