A Comparative Study of Entecavir and Tenofovir Alafenamide on Quantitative HBsAg Reduction in Patients With CHB

Entecavir (ETV) and tenofovir alafenamide (TAF) are two first-line nucleos(t)ide analogs used for the treatment of chronic hepatitis B (CHB), each offering potent antiviral activity and a high barrier to resistance. We aimed to directly compare the effects of ETV and TAF on the quantitative reduction of hepatitis B surface antigen (HBsAg) levels in CHB patients. We screened 1342 consecutive CHB patients treated with ETV or TAF at our center between January 2007 and December 2021. In total, 493 patients were included in the final analysis (ETV, n = 169; TAF, n = 324). The primary endpoint was the difference in quantitative HBsAg reduction between the two groups at 12 and 24 months. Secondary endpoints included changes in the estimated glomerular filtration rate (eGFR), phosphorus, and low-density lipoprotein (LDL)-cholesterol levels. Although the absolute median HBsAg reduction was not significantly different between the TAF and ETV groups (p > 0.05), more patients in the TAF group achieved > 10% quantitative HBsAg decline at 12 months (63.0% vs. 55.8%, p = 0.009) and 24 months (81.7% vs. 65.1%, p < 0.001). The TAF group demonstrated a stable median eGFR (mL/min/1.73 m²) change compared to the ETV group (0.0 vs. -6.0, p = 0.003) at 24 months. The TAF group showed better preservation of serum phosphorus levels at 24 months (p = 0.003). The changes in LDL-cholesterol levels were not significantly different between the two groups. In CHB patients, TAF showed a significantly higher proportion of quantitative HBsAg reduction and a superior renal safety profile than ETV, without significant differences in LDL-cholesterol changes.