Do Tenofovir and Entecavir affect renal function in patients with chronic hepatitis B (CHB)? A two-year observational study from a single Australian centre. [Journal of Gastroenterology and Hepatology]

Abstract

Background Tenofovir (TDF) and Entecavir (ETV) are nucleos(t)ide (NUC) analogues which are potent inhibitors of hepatitis B virus. However, the long-term effect of TDF on renal function in CHB patients remains unclear. Aims To compare the incidence, severity and clinical significance of changes in renal function over 2 years amongst CHB patients treated with TDF 300 mg daily or ETV 0.5 mg or 1.0 mg daily versus an untreated cohort. Methods We retrospectively identified 124 patients treated with either ETV (n = 74) or TDF+/- LMV (n = 50) for a minimum of 2 years. 73 untreated CHB patients were used as controls. Renal function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula (MDRD) at baseline, 6, 12 and 24 months. Exclusion criteria included concomitant use of potential nephrotoxins, decompensated cirrhosis and previous NUC exposure apart from lamivudine if renal function was normal upon commencement of TDF. Baseline demographics, MELD score, presence of cirrhosis and risk factors for renal impairment were recorded. Outcomes assessed included kidney function (decline in eGFR >=40% and change in eGFR over time) and dose adjustment or cessation of either therapy. Analysis was performed using a mixed linear model to incorporate repeated measures. Results Baseline characteristics were closely matched between the three cohorts (p = NS). Older age (p = 0.0043) and cirrhosis (p < 0.0001) were more prevalent in the ETV group. The proportion of patients with >=40% reduction in eGFR from baseline was 3.92% in the TDF +/- LMV group vs. 2.7% in the ETV group (p = NS). In the univariate mixed linear model, compared to control subjects at baseline, eGFR at 2 years declined in the ETV group by -7.6 ml/min (95% CI -15.8-+0.6, p = 0.07) and -8.7 ml/ min (CI -18.3-+1.0, p = 0.08) in the TDF +/- LMV group while in the control it remained stable at +7.4 ml/min (CI 0.78 - 14.1, p = 0.03). After adjustment for age, gender, hypertension, diabetes and cirrhosis, eGFR decline at 2 years was attenuated in the ETV group (-1.8 ml/min, -10.2 -6.5, p = 0.67) but not in the TDF group (-6.5 (-16.1-+3.0, p = 0.18) while in the control it remained higher 7.2 ml/min (0.58-13.8, p = 0.03). There were no episodes of treatment cessation or dose adjustment. Conclusion In this single centre study of 124 treated CHB patients, there was a suggestion of decline in renal function in both ETV and TDF treated patients. However, we did not observe any significant changes in eGFR over 2 years of treatment. Observation in a real world cohort over a longer period may provide further insights into the potential renal complications of NUC therapy. (Table presented).