Abstract
Long-term nucleos(t)ide analogue (NA) therapy is required for chronic hepatitis B (CHB), and drug-related renal and bone toxicities remain a major clinical concern. The real-world differences in renal and bone safety between tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), as well as their relationship with antiviral efficacy, need further validation in local populations. We conducted a single-center retrospective cohort study enrolling 102 adult CHB patients (TAF, n = 52; TDF, n = 50) who initiated therapy within the past 3 years and were followed up for 6 and 12 months. The primary outcomes were changes in estimated glomerular filtration rate (ΔeGFR, mL/min/1.73 m²) and lumbar spine bone mineral density (% change). Secondary outcomes included undetectable hepatitis B virus DNA rate, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion. Safety endpoints comprised hypophosphatemia, proteinuria, acute kidney injury, grade ≥ 3 adverse events, and treatment discontinuation. Group comparisons were performed using Welch's t test or χ²/Fisher's exact test, and sensitivity analyses were conducted using propensity score matching. Baseline characteristics were comparable between groups after propensity score matching. At 6 months, changes in estimated glomerular filtration rate did not differ significantly (0.78 ± 4.91 vs -0.39 ± 5.00; P = .236), but at 12 months, TAF showed superior renal preservation (1.22 ± 5.81 vs -1.58 ± 5.68; P = .016). Lumbar bone mineral density changes were similar at 6 months (0.27 ± 1.43% vs -0.20 ± 1.53%; P = .113) but favored TAF at 12 months (0.56 ± 1.75% vs -0.47 ± 1.97%; P = .006). Virological outcomes, including hepatitis B virus DNA suppression and hepatitis B e antigen seroconversion, were comparable at both time points. Alanine aminotransferase normalization showed a nonsignificant trend favoring TAF at 12 months (73.08% vs 88.00%; P = .058). TAF was associated with markedly lower rates of hypophosphatemia (1.92% vs 28.00%; P < .001) and less proteinuria at 6 months (3.85% vs 16.00%; P = .039). In this retrospective cohort, TAF demonstrated significantly better renal and bone safety profiles than TDF after 12 months of treatment, while achieving equivalent antiviral efficacy. For CHB patients at risk of renal or bone impairment, TAF may represent a safer long-term therapeutic option.