Abstract
BACKGROUND: For individuals with chronic hepatitis B (CHB) at higher risk of nephrotoxicity, entecavir (ETV) and tenofovir alafenamide (TAF) are recommended antiviral options. This study aimed to investigate kidney safety among treatment-naïve individuals with CHB receiving TAF versus ETV. METHOD: Treatment-naïve individuals with CHB receiving either TAF or ETV from July 2019 to December 2020 were included. Follow-up data on estimated glomerular filtration rates (eGFR) were collected. Factors related to chronic kidney disease (CKD) development were analyzed by Cox regression analysis. Generalized additive mixed model (GAMM) was employed to investigate temporal eGFR changes and the association between the extent of follow-up eGFR change and antiviral agents. RESULTS: 466 treatment-naïve individuals with CHB were included, with 296 in the ETV group and 170 in the TAF group. In the subgroup of individuals with a baseline eGFR higher than 90 mL/min/1.73 m(2), 13.9% in the ETV group developed CKD, compared to 9.8% in the TAF group (p = 0.304). Multivariable Cox analysis demonstrated that male (hazard ratio (HR) 2.72; 95% confidence interval (CI) [1.02-7.25]; p = 0.045) and baseline eGFR (HR 0.86; 95% CI [0.82-0.90]; p < 0.001) were significantly associate with the CKD development. GAMM revealed that eGFR initially decreased and then stabilized around week 40. Every 12 weeks, the TAF group exhibited an overall lower rate of eGFR decline compared to the ETV group, with an adjusted difference of 0.38 mL/min/1.73 m(2) (95% CI [0.11-0.65], p = 0.006). The difference remained significant in males and patients over 35 years old. CONCLUSION: The kidney safety profile of TAF among treatment-naïve individuals with CHB was comparable to that of ETV, without significant difference in developing CKD. Stratified analyses further revealed that TAF demonstrated superior kidney benefits compared to ETV specifically in males or patients aged over 35 years.