Impact of Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide or Entecavir in Older Patients with Chronic Hepatitis B.

Authors

Federico Cesanelli, Ottavia Nozza, Federica Gottardi, Francesca Mosti, Serena Zaltron, Giorgio Tiecco, Irene Scarvaglieri, Angiola Spinetti, Francesco Castelli, Eugenia Quiros-Roldan

Published in

Infectious diseases and therapy. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

Tenofovir disoproxil fumarate (TDF) is highly effective for chronic hepatitis B (CHB) but may induce progressive renal impairment and proximal tubular dysfunction. Switching to tenofovir alafenamide (TAF) or entecavir (ETV) may reduce TDF-related nephrotoxicity. This study evaluated renal and metabolic changes before and after switching from TDF to TAF or ETV in a real-world cohort of older patients.
This retrospective longitudinal cohort study included adults with CHB who switched from TDF to TAF or ETV at a tertiary center (2012-2023). Eligible patients had ≥ 2 years of TDF treatment and ≥ 2 years of post-switch follow-up. Those with virological failure, major coinfections, or non-HBV-related kidney disease were excluded. Clinical and laboratory data were collected at 6-month intervals from 2 years before to 4 years after switching. Biomarker trajectories were analyzed using linear mixed-effects models with time centered at switch comparing treatments and with multivariable adjustment for key confounders.
A total of 102 patients were included (TAF n = 82; ETV n = 20), mean age 72 ± 10 years, 72% male. All patients had undetectable HBV-DNA at switch. During TDF therapy, serum creatinine showed a non-significant increasing trend (β = + 0.008 mg/dL/year, p = 0.24), which persisted after switching (β = + 0.009 mg/dL/year, p = 0.07), with no significant difference between groups. Serum phosphate declined during TDF in the ETV group (β = - 0.175 mg/dL/year, p = 0.002) and showed a significant increase after switching (β = + 0.111 mg/dL/year, p = 0.031) while the TAF group remained stable throughout. Total cholesterol ishowed a significant immediate increase at the time of switch (+ 18.3 mg/dL, 95% CI 11.0-25.6, p < 0.001), with no significant difference between TAF and ETV.
Unlike previous studies reporting clear creatinine improvement after switching from TDF, this cohort did not show a statistically significant reduction in creatinine levels after the switch although an attenuation of creatinine progression and recovery of phosphate levels were observed, suggesting mitigation of TDF-related renal and tubular toxicity.

PMID:
42479363
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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