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

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.