Long-Term Renal Safety Between Patients With Chronic Hepatitis B Receiving Tenofovir vs. Entecavir Therapy: A Multicenter Study

Background Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Methods Treatment-naïve CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. Results At beginning of observation, ETV group had unfavorable conditions than TDF group: lower eGFR and higher FIB-4 and APRI than TDF group (all P<0.001). After 6 years antiviral therapy, the mean eGFR in ETV group (n=1,793) was maintained (96.0 at first year to 95.6 mL/min/1.73 m2 at sixth year; AAPC -0.09%; P=0.322), whereas that in TDF group (n=1,240) significantly decreased annually (101.9 at first year to 96.9 mL/min/1.73 m2 at sixth year; AAPC -0.88%; P<0.001). Notably, in TDF group, even patients without diabetes (AAPC -0.80%; P=0.001) or hypertension (AAPC -0.87%; P=0.001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC -1.59%; p=0.011) or hypertension (AAPC -1.00%; p=0.002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, P<0.001), along with eGFR<60 mL/min/1.73 m2, serum albumin<3.5 mg/dL, and hypertension, were independently associated with ongoing renal dysfunction, defined as a negative slope of the mean eGFR change. Conclusions Compared to ETV, long-term TDF treatment induced slow, but progressive renal dysfunction. Although the annual eGFR change by TDF was small, careful monitoring is necessary, especially in patients requiring life-long therapy.