Atherosclerotic Cardiovascular Risk in Patients with Chronic Hepatitis B: Tenofovir Disoproxil Fumarate Vs. Tenofovir Alafenamide: A Korean Nationwide Study

Tenofovir alafenamide (TAF) exhibits antiviral efficacy comparable to tenofovir disoproxil fumarate (TDF). Nonetheless, concerns persist regarding TAF's impact on the lipid profile and potential atherosclerotic cardiovascular disease (ASCVD) risk. This study evaluated long-term ASCVD risk in patients with chronic hepatitis B (CHB) treated with TAF or TDF using Korean National Health Insurance Service claims data. We retrospectively analyzed treatment-naïve patients with CHB who received TAF or TDF between 2017 and 2022. Cumulative ASCVD incidence was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score (PS) matching and Cox regression were used to minimize confounding and identify ASCVD risk factors, respectively. Among 44,714 patients with CHB, 16,120 (36.1%) received TAF, whereas 28,594 (63.9%) received TDF. Over a median follow-up period of 3.0 years, ASCVD occurred in 817 patients (630 TDF-treated and 187 TAF-treated), with an annual incidence of 6.18/1000 patient-years (PYs). TAF was associated with lower ASCVD risk than TDF (4.60 vs. 6.88/1000 PYs; p < 0.001), a trend maintained after PS matching (4.67 vs. 6.67/1000 PYs; hazard ratio 0.70; p < 0.001) among 15,169 matched pairs. Older age, male sex, hypertension, current smoking, and aspartate aminotransferase ≥ 40 U/L were risk factors for ASCVD development. Despite concerns about lipid metabolism, TAF did not increase ASCVD risk compared with TDF, offering reassurance for clinicians selecting antiviral therapies for patients with CHB.