Background and Aims: Entecavir (ETV) and tenofovir alafenamide (TAF) are the preferred agents in patients with predisposing factors for nephrotoxicity, but no studies to date have directly compared the renal safety of the two antiviral agents. Hence, we compared the risk of kidney function decline among patients with treatment-naïve chronic hepatitis B (CHB) treated with ETV or TAF. Methods: This study included 1988 patients with treatment-naïve CHB who were treated with ETV (n = 1839) or TAF (n = 149) between 2007 and 2020 for ETV and between 2017 and 2020 for TAF. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months. Results: A 1:1 propensity score match yielded 149 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.6 ml/min/1.73 m2 vs. 101.3 ml/min/1.73 m2 in the ETV and TAF groups respectively. A total of 61 patients developed a progression in CKD stage ≥ 1, of which 47 and 14 patients were from the ETV- and TAF-treated groups respectively (19.9 vs. 5.1 per 1000 person-years; p <.001). The risk of progression in CKD stage ≥1 was significantly higher in patients treated with ETV, even when adjusted for potential confounders (adjusted hazard ratio 4.05; 95% CI 2.14–7.68; p <.001). Conclusions: ETV was associated with a higher risk of kidney function decline than TAF in patients with treatment-naïve CHB. Therefore, further prospective randomized studies are needed.
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