Prior studies on the effects of tenofovir alafenamide (TAF) in liver transplant recipients were found to be limited to small-scale only.^1-2 However, a recent large-scale, multicenter study conducted by Liu JK et al. published in Clinical Gastroenterology and Hepatology compared renal outcomes among liver transplant recipients with chronic hepatitis B virus (HBV) treated with TAF, tenofovir disoproxil fumarate (TDF) or entecavir (ETV).¹

The nucleos(t)ide analogs ETV, TAF and TDF have been clinically proven to be safe and efficacious for the treatment of chronic HBV and HBV-related cirrhosis.³ However, the development of renal dysfunction and recurrence of viral hepatitis after liver transplantation can cause a variety of adverse outcomes, including graft failure and decreased patient survival.^4,5 Approximately 22% of liver transplant recipients develop chronic kidney disease (CKD) within 5 years after transplantation, and the risk increases to approximately 30%-50% after 10 years following transplantation, which can be contributed by the nephrotoxic immunosuppressive drug treatments.^1,4,6

In this multicenter retrospective cohort study, 298 post-liver transplant recipients were recruited from 5 centers from the United States, Singapore and Japan in 2005-2020.¹ Data were obtained through medical records of each patient, using a unified structured data frame at each center.¹ The mean follow-up period was 21.95 ± 4.63 months.¹

The participants were grouped by their antiviral monotherapy treatment: 1) TAF (N=112); 2) TDF (N=51); and 3) ETV (N=135).¹ The key characteristics of this study population: 1) male (73.83%); 2) Asian (75.84%); 3) diagnosis of HBV pre-Liver transplantation (91.28%), with the remaining having HBV core antibody grafts; and 4) received tacrolimus-based immunosuppression (94.97%).¹ The age of TAF patients was 60.61 ± 11.09 years, while TDF patients were 57.29 ± 10.99 years and ETV patients were 57.04 ± 10.12 years (p=0.02).¹ The primary outcome was to analyze the changes in renal function, in terms of CKD stage in the liver transplant recipients.¹

Hypertension was examined and the TAF-treated group (66.07%) had the highest percentage of patients having hypertension, then the TDF-treated group (62.75%), and lastly the ETV-treated group (51.11%) (p=0.048).¹ Additionally, the TAF-treated group had the lowest mean baseline estimated glomerular filtration rate (eGFR) (64.73 ± 25.09 mL/min/1.73m² ), followed by the TDF-treated group (66.59 ± 25.84  mL/min/1.73m² ), and lastly the ETV-treated group (74.34 ± 28.45mL/min/1.73 m² ) (p=0.01).¹

In the TAF-treated group, a greater percentage of patients had mild renal dysfunction (CKD stage 2; 42.86%) to moderate/severe renal dysfunction (CKD stage 3/5, 42.86%) as compared with normal renal function (CKD stage 1, 14.29%).¹ Additionally, there were no substantial changes in CKD stage distribution in the TAF-treated group from baseline to the 24-month follow-up and a comparative trend was seen in the TDF-treated group.¹ Contrastingly, the proportion of ETV-treated patients with normal renal function had decreased to 18.18% from 35.56% at baseline (p=0.002), and the proportion of patients with mild renal dysfunction (CKD stage 2) increased from 32.59% at baseline to 49.59% at the 24-month follow-up (p=0.006).¹

When comparing eGFR among the 3 monotherapy groups, the TAF-treated group had the smallest decrease (unadjusted eGFR decreased 1.46mL/min/1.73m²) in comparison with those on TDF (2.97mL/min/1.73m²) or ETV (4.57mL/min/1.73m²).¹ TAF-treated patients also showed significant stability in CKD stage categories (1,2 and 3-5) when evaluated for CKD stage migration.¹ Contrastingly, the ETV-treated group demonstrated a significant decrease in the percentage of patients with normal renal function and an increase in patients with mild renal dysfunction.¹ The TDF-treated group demonstrated a greater decrease in patients with normal renal function from baseline to 24-month follow-up (23.53% at baseline to 14.29%) as compared with the TAF-treated patients (14.29% to 11.11%).¹

In summary, the TAF-treated group had lesser baseline renal function. It was the oldest group, having higher hypertension rates, but maintained eGFR rates that were similar to the TDF-treated group.¹ Furthermore, TAF-treated patients demonstrated a smaller decline in eGFR throughout the 24-month follow-up interval in comparison to the TDF- and ETV-treated groups.¹ This multicenter cohort study provided short-term data in a large-scale setting on the renal outcomes in liver transplant recipients with antiviral therapies, highlighting TAF as more beneficial.¹ However, further studies with longer follow-up periods are needed to provide long-term outcome data on the evaluation of TAF within this framework.¹