Li Xuan, Wu Qiang, Huang Fang, Lai Changxiang, Chen Fengjuan, Meng Juan, Wang Fang, Zeng Hui, Zhang Lina
Department of Liver Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China.
Phase I Clinical Trial Centre, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China.
PeerJ. 2025 Aug 26;13:e19901. doi: 10.7717/peerj.19901. eCollection 2025.
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.
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.
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, 13.9% in the ETV group developed CKD, compared to 9.8% in the TAF group ( = 0.304). Multivariable Cox analysis demonstrated that male (hazard ratio (HR) 2.72; 95% confidence interval (CI) [1.02-7.25]; = 0.045) and baseline eGFR (HR 0.86; 95% CI [0.82-0.90]; < 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 (95% CI [0.11-0.65], = 0.006). The difference remained significant in males and patients over 35 years old.
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.
对于有更高肾毒性风险的慢性乙型肝炎（CHB）患者，恩替卡韦（ETV）和替诺福韦艾拉酚胺（TAF）是推荐的抗病毒治疗选择。本研究旨在调查初治CHB患者接受TAF与ETV治疗时的肾脏安全性。
纳入2019年7月至2020年12月期间初治的接受TAF或ETV治疗的CHB患者。收集估算肾小球滤过率（eGFR）的随访数据。通过Cox回归分析慢性肾脏病（CKD）发生的相关因素。采用广义相加混合模型（GAMM）研究eGFR的时间变化以及随访期间eGFR变化程度与抗病毒药物之间的关联。
纳入466例初治CHB患者，其中ETV组296例，TAF组170例。在基线eGFR高于90 mL/min/1.73 m²的亚组中，ETV组13.9%发生CKD，TAF组为9.8%（P = 0.304）。多变量Cox分析表明，男性（风险比（HR）2.72；95%置信区间（CI）[1.02 - 7.25]；P = 0.045）和基线eGFR（HR 0.86；95% CI [0.82 - 0.90]；P < 0.001）与CKD发生显著相关。GAMM显示，eGFR最初下降，然后在第40周左右趋于稳定。每12周，TAF组eGFR下降的总体速率低于ETV组，校正差异为0.38 mL/min/1.73 m²（95% CI [0.11 - 0.65]，P = 0.006）。在男性和35岁以上患者中，这种差异仍然显著。
初治CHB患者中TAF的肾脏安全性与ETV相当，发生CKD无显著差异。分层分析进一步显示，与ETV相比，TAF在男性或35岁以上患者中具有更好的肾脏保护作用。
