Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Abstract

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

“…These agents strongly inhibit the HBV polymerase, suppressing viral replication. The most recently developed NA, TAF, is a TDF pro‐drug that shares the same mechanism of action as TDF with improved bioavailability …”

“…TDF and ETV are not contraindicated in patients with underlying kidney disease, but patients should be closely monitored because of a higher associated risk of adverse effects. TAF reduces TDF plasma levels and systemic exposure by up to 90% resulting in a better safety profile …”

“…Fanconi syndrome has been reported in isolated cases. Tubular injury and BMD loss (as well as Fanconi syndrome) seem to be reversible following TDF withdrawal and switching to ETV or TAF . Long‐term ETV has been associated with a low incidence of lactic acidosis (<0.3%) .…”

“…The most recently developed NA, TAF, is a TDF pro-drug that shares the same mechanism of action as TDF with improved bioavailability. 5 Both ETV and TDF have been shown to be more effective than low-and intermediate-barrier NAs in phase III trials and real-life studies in CHB patients with or without compensated cirrhosis. 2 No significant differences in antiviral efficacy were detected between these two agents.…”

“…Tubular injury and BMD loss (as well as Fanconi syndrome) seem to be reversible following TDF withdrawal and switching to ETV or TAF. 5,15 Long-term ETV has been associated with a low incidence of lactic acidosis (<0.3%). 6 EASL does not recommend TDF as first-line treatment because of its safety profile in individuals older than 60 with kidney impairment (CrCl <60 mL/min, albuminuria, serum phosphate <2.5 mmol/dL) or bone disease.…”