Do any of the described cases—treatment‑naïve patients with reduced estimated glomerular filtration rate starting entecavir or tenofovir alafenamide (TAF), and treatment‑experienced patients on tenofovir disoproxil fumarate (TDF) being switched to entecavir or TAF—have leukopenia?

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Last updated: October 3, 2026 • View editorial policy

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No Evidence of Leukopenia in Any of the Described Cases

Based on the available evidence, none of the described clinical scenarios—treatment-naïve patients with reduced eGFR starting entecavir or TAF, or treatment-experienced patients on TDF being switched to entecavir or TAF—are associated with leukopenia. The provided guidelines and clinical trial data focus exclusively on renal function (eGFR changes), bone mineral density, and hepatic outcomes, with no mention of leukopenia as an adverse effect in these populations 1, 2.

Key Safety Profiles from the Evidence

Renal and Bone Effects (Not Leukopenia)

The KASL guidelines extensively document adverse effects of nucleos(t)ide analogues in patients with reduced renal function, but these are limited to:

  • Renal dysfunction: Decreased eGFR, proteinuria, hypophosphatemia
  • Bone effects: Decreased bone mineral density, osteopenia, osteoporosis
  • Other specific toxicities: Lactic acidosis, Fanconi syndrome (with TDF/adefovir), myopathy (with telbivudine/clevudine), pancreatitis (with lamivudine) 3

Leukopenia is notably absent from these documented adverse effects.

Treatment-Naïve Patients with Reduced eGFR

For treatment-naïve patients with eGFR <60 mL/min/1.73 m², the guidelines recommend entecavir, TAF, or besifovir over TDF 1. The evidence shows:

  • Entecavir: Less impact on renal function and bone density compared to TDF, with no leukopenia reported 2
  • TAF: Superior renal and bone safety compared to TDF, with improved eGFR in patients with baseline renal impairment 4, 5

Treatment-Experienced Patients Switching from TDF

When patients on TDF develop renal dysfunction or are at risk, switching to entecavir or TAF results in:

  • Improved eGFR: Recovery of renal function after switching from TDF to either TAF or entecavir 1, 6
  • Bone density recovery: Improvement in bone mineral density after switching from TDF 2
  • No hematologic toxicity: No leukopenia or other blood count abnormalities documented 6, 7

Clinical Implications

The absence of leukopenia in these scenarios is clinically significant because:

  1. Monitoring focus should be on renal function: Regular assessment of eGFR, proteinuria, and serum phosphorus is essential 1, 2
  2. Bone health surveillance: Particularly in patients with risk factors for osteoporosis 2
  3. No routine CBC monitoring for leukopenia: Unlike some other antiviral agents, these NUCs do not require hematologic monitoring for leukopenia

Dose Adjustments Based on Renal Function (Not Leukopenia)

The guidelines provide specific dose adjustments for creatinine clearance, not for blood counts 2:

  • Entecavir: Requires dose adjustment if CrCl <50 mL/min
  • TAF: Not recommended if CrCl <15 mL/min
  • TDF: Requires dose adjustment if CrCl <50 mL/min

None of these adjustments are related to leukopenia.

References

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