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Introduction <p>Tenofovir disoproxil fumarate (TDF) is highly effective for chronic hepatitis&#xa0;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.</p> Methods <p>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&#xa0;years of TDF treatment and ≥ 2&#xa0;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&#xa0;years before to 4&#xa0;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.</p> Results <p>A total of 102 patients were included (TAF <i>n</i> = 82; ETV <i>n</i> = 20), mean age 72 ± 10&#xa0;years, 72% male. All patients had undetectable HBV-DNA at switch. During TDF therapy, serum creatinine showed a non-significant increasing trend (<i>β</i> = + 0.008&#xa0;mg/dL/year, <i>p</i> = 0.24), which persisted after switching (<i>β</i> = + 0.009&#xa0;mg/dL/year, <i>p</i> = 0.07), with no significant difference between groups. Serum phosphate declined during TDF in the ETV group (<i>β</i> = − 0.175&#xa0;mg/dL/year, <i>p</i> = 0.002) and showed a significant increase after switching (<i>β</i> = + 0.111&#xa0;mg/dL/year, <i>p</i> = 0.031) while the TAF group remained stable throughout. Total cholesterol ishowed a significant immediate increase at the time of switch (+ 18.3&#xa0;mg/dL, 95%&#xa0;CI 11.0–25.6, <i>p</i> &lt; 0.001), with no significant difference between TAF and ETV.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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

摘要

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.