HERACLIS‐TAF: a multi‐centre prospective cohort study on 2‐year safety and efficacy of tenofovir alafenamide in patients with chronic hepatitis B with renal and/or bone disorders or risks

Abstract

Summary Background Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. Aims To assess predictors of eGFR changes and other safety and efficacy outcomes during 24‐month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. Methods Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. Results TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p < 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p < 0.001), increased at 12 months and remained stable at 24 months (p ≤ 0.001). An increase in eGFR of >3 ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30–60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month‐12/24 (p < 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p = 0.001). Conclusions In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12‐24 months of TAF treatment, especially in patients with baseline eGFR 30–60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression.

Editorial: changes in renal function and bone mineral density after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B

“…Another study also found that most patients with eGFR <60 ml/min who had renal deterioration during TDF reversed to eGFR increase after 1 year of TAF 6 . Regarding bone safety, this study showed that median BMD did not change significantly from baseline to 12 months, but improved at 24 months of TAF 8 . Two recent studies showed an improvement in BMD in both hip and spine at week 24 after switching to TAF 3,7 …”

“…Papatheodoridis et al have reported that eGFR increased at 12 months after switching to TAF and remained stable at 24 months 8 . The main finding is that TAF seems to significantly improve eGFR only in patients with eGFR 30–60 ml/min at initiation, but not in those with eGFR >60 or <30 ml/min.…”

“…6 Regarding bone safety, this study showed that median BMD did not change significantly from baseline to 12 months, but improved at 24 months of TAF . 8 Two recent studies showed an improvement in BMD in both hip and spine at week 24 after switching to TAF . 3,7 We suggest that patients with risks of renal dysfunction and bone disease are suitable for TAF .…”

“…7 Papatheodoridis et al have reported that eGFR increased at 12 months after switching to TAF and remained stable at 24 months. 8 The main finding is that TAF seems to significantly improve eGFR only in patients with eGFR 30-60 ml/min at initiation, but not in those with eGFR >60 or <30 ml/min. One recent study AP&T correspondence columns are restricted to invited editorials and letters discussing papers that have been published in the journal.…”

Editorial: changes in renal function and bone mineral density after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in chronic hepatitis B patients—author's reply

“…Tseng and Chen for their thoughtful editorial 1 commenting on our recent HERACLIS-TAF prospective cohort study, which assessed the changes of estimated glomerular filtration rate (eGFR) and other safety and efficacy parameters during 24-months of tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB) treated in Greece. 2 I agree with their comments and approach, but I would like to clarify a few issues in an effort to explain some seemingly conflicting reports on changes of safety parameters during TAF therapy. The study included patients with CHB who were mostly switched from tenofovir disoproxil fumarate (TDF) to TAF (88%) because of impaired renal function (eGFR <60 ml/min: 46%), and/or low serum phosphate (<2.5 mg/dl: 22%), and/or osteoporosis (T-score <−2.5: 31%).…”