Background and aims: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). Methods: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). Results: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11–1.43) was associated with higher risk of worsening renal function. Conclusion: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.
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