Evaluation of renal function with TAF in liver transplant patients: A large-scale multicenter study

14 Jun 2022

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

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