BACKGROUND: Long term renal safety of antiviral agents against hepatitis B virus (HBV) has been debated.AIM: To compare longitudinal trends of renal function among HBV mono-infected patients receiving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and adefovir (ADV) in comparison to untreated subjects.METHODS: A retrospective cohort consisting of 815 patients with chronic HBV infection was constructed. Serial estimated glomerular filtration rate (eGFR) was compared to the expected rate of age-dependent decline in eGFR, derived from the National Health and Nutrition Examination Survey (NHANES) data. Generalised estimating equations and linear mixed-effects models were used to compare trends in eGFR (in mL/min/1.73m2 as a "unit").RESULTS: In NHANES data (n=23051), each year of age was associated with a 0.86 unit decrease in eGFR in subjects without hypertension and 0.96 units with hypertension. The Stanford cohort consisted of patients who received ETV (n=207), TDF (n=191), ADV (n=46) or no therapy (n=371). After a median follow-up 4.0 (interquartile range: 1.9-6.5) years, there was no significant difference in the expected and observed rates of eGFR decline in untreated HBV patients. Patients receiving antiviral treatment experienced steeper reduction in renal function than expected. In the multivariable model, ETV was associated with eGFR loss at 1.81 units per year (P=0.06, compared to untreated patients). TDF- and ADV-treated patients experienced significantly higher rate of eGFR loss at 2.21 and 2.63 units per year, respectively (both P<0.01).CONCLUSION: In this longitudinal cohort study, HBV patients receiving antiviral therapy, particularly TDF and ADV, experienced more rapid loss in eGFR.
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