Yu Li,1,* Ya-Wei Li,2,* Ying Gao3 

1Department of Infectious Diseases, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi Province, 710068, People’s Republic of China; 2Division of Medical Affairs, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, Hubei Province, 442099, People’s Republic of China; 3Department of Hematology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi Province, 710068, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ying Gao, Department of Hematology, Shaanxi Provincial People’s Hospital, 256 West Youyi Road, Xi’an, Shaanxi Province, 710068, People’s Republic of China, Email yingg7727@163.com

Background: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide(TAF) are first-line nucleos(t)ide analogs (NUCs) with chronic hepatitis B (CHB). This study aimed to assess the renal safety profile in NUC-experienced CHB patients who received ETV, TDF or TAF therapy.
Methods: This retrospective observational cohort study investigated factors related to renal function in 154 patients with NUC-experienced CHB who received ETV, TDF, and TAF therapy for 48 weeks. Changes in UREA, uric acid (UA), creatinine (Cr), and estimated glomerular filtration rate (eGFR) were analyzed using a one-way analysis of variance. A linear mixed-effects model for repeated measures was used to evaluate the correlation between baseline information and eGFR changes 48 weeks following treatment initiation. The model considered sex, baseline age, viral load, aminotransferases, renal function, and treatment group as fixed effects, and incorporated random effects for individual subjects.
Results: There were no significant differences in UA or Cr levels during therapy over time. The eGFR level was elevated in ETV-treated patients (117.5 ± 16.65 mL/min/1.7m2 vs 109.8 ± 15.69 mL/min/1.7m2, P=0.027), whereas it did not change significantly in TDF- (123.6 ± 28.54 mL/min/1.7m2 vs 115.5 ± 20.44 mL/min/1.7m2, P=0.070) and TAF-treated (121.6 ± 23.44 mL/min/1.7m2 vs 113.4 ± 16.90 mL/min/1.7m2, P=0.053) patients. Younger patients (< 30 years) and those with higher HBV DNA (> 7 log10IU/mL) and lower alanine aminotransferase levels (< 5 × upper limit of normal) showed a significant improvement in eGFR elevation during NUCs therapy. The linear mixed-effects model showed that the baseline HBV DNA level was an important positive predictor of eGFR elevation at 48 weeks following treatment initiation (estimate was 1.437 and 2.449, P< 0.001).
Conclusion: In real-life experience, ETV, TDF, and TAF therapy may not be associated with eGFR changes in NUC-experienced CHB patients without baseline renal impairment.

Keywords: chronic hepatitis B, nucleos(t)ide analogs, antiviral, renal function, linear mixed-effects model