Safety and efficacy of tenofovir alafenamide in preventing hepatitis B virus recurrence after liver transplantation in patients with chronic kidney disease maintained on tenofovir disoproxil fumarate: Results from a phase 2 randomized trial.

Tenofovir disoproxil fumarate (TDF) effectively prevents hepatitis B virus (HBV) reactivation after orthotopic liver transplantation (OLT) in patients with chronic HBV infection. Tenofovir alafenamide (TAF) demonstrated efficacy noninferior to TDF with improved renal and bone safety in phase 3 studies but has not been studied in patients who have undergone OLTs. In a phase 2 open-label trial, 51 patients with chronic HBV infection maintained on TDF therapy after OLTs with stage ≥ 2 chronic kidney disease (CKD) were randomized to switch to TAF (n = 26) or continue TDF (n = 25). After 48 weeks (W) of randomized treatment, all patients received TAF through W192; 90% completed the study. Groups were evenly matched: 51% aged > 60 years; 78% on calcineurin inhibitors; 53% with an estimated glomerular filtration rate by CKD Epidemiology Collaboration creatinine (eGFRCKD-EPICr) value of < 50 mL/min/1.73 m2. No patient had HBV reactivation or experienced a grade 3/4 adverse event or serious adverse event deemed treatment-related. At W48, median eGFRCKD-EPICr value changes were 4.4 vs 0.2 mL/min/1.73 m2 (P = .414), and median percent increases in bone mineral density were greater for TAF vs TDF at hip (P = .006) and spine (P = .024). Hip bone mineral density increases were greater with TAF with an eGFRCKD-EPICr value of < 50 mL/min/1.73 m2 (P = .008) and calcineurin inhibitor use (P = .010). TAF was safe and effective through W192 post-OLT.