Long-term safety of treatment with hepatitis B virus (
HBV) polymerase inhibitors is a concern.
Adefovir dipivoxil (ADV)
therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination
therapy with nucleos(t)ide analogues and
interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination
therapy with
peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either
drug alone in patients with
hepatitis B/D
co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International
Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of
therapy with PegIFNα-2a+ADV vs either
drug alone in 90 patients with
chronic hepatitis B/D
co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of
therapy GFR values were significantly lower in patients receiving
adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving
adefovir alone vs combination treatment. Twenty-four weeks
after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥ 20% was observed more often in patients during
adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan-Meier analysis.
Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in
chronic hepatitis B/D
co-infection did not lead to any further impairment of kidney function.