Tenofovir alafenamide rivals TDF, ETV at preserving renal function after liver transplant

Tenofovir alafenamide (TAF) yields comparable renal outcomes to tenofovir disoproxil fumarate (TDF) in liver transplant (LT) recipients, according to a study presented at The Liver Meeting Digital Experience 2021 by the American Association for the Study of Liver Diseases (AASLD 2021).

Moreover, compared with TDF and entecavir (ETV), TAF demonstrates the greatest stability in estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) stage categorizations.

The current multicentre retrospective cohort study included 298 LT recipients (mean age 58.4±10.7 years, 73.83 percent men), 112 of whom were treated with TAF, 51 with TDF, and 135 with ETV. Most (75.84 percent) were of Asian ethnicity and had chronic hepatitis B before transplantation. TAF recipients tended to be older (p=0.02), had the lowest mean eGFR at baseline (p=0.01), and were more likely to have hypertension (p=0.048) than TDF and ETV counterparts.

Despite significant baseline differences, the TAF arm saw the greatest stability in renal parameters over 24 months of follow-up, with a mean unadjusted eGFR decline of 1.46 mL/min/1.73 m². In contrast, the mean drops in eGFR in the TDF and ETV arms were 2.97 and 4.57 mL/min/1.73 m², respectively. In turn, by the end of follow-up, the significant among-group difference in eGFR had been attenuated (p=0.15). [Liu JK, et al, The Liver Meeting 2021]

The researchers also noted greater stability in CKD staging in the TAF group. Despite a higher baseline prevalence of stage 2 and 3–5 CKD, TAF recipients saw no significant worsening of CKD stages over 24 months of follow-up. The same was true for TDF. Meanwhile, there was a significant increase in stage 2 CKD (p=0.006) in the ETV arm, accompanied by a significant drop in the proportion of patients with normal renal function (p=0.002).

Multivariable generalized estimating equation (GEE) analysis was then performed to identify potential predictors of deteriorating renal function. After controlling for age, sex, hypertension or diabetes, hepatitis B virus treatment, baseline eGFR, and time from liver transplantation, age emerged as a significant, independent, and inverse correlate of mean eGFR (coefficient, –0.68, 95 percent confidence interval [CI], –0.85 to –0.50; p<0.001).

Other notable predictors included the male sex (coefficient, 4.41, 95 percent CI, 0.74–8.09; p=0.02), as well as baseline eGFR 60–89 mL/min/1.73 m² (coefficient, –16.29, 95 percent CI, –20.77 to –11.81; p<0.001) and <60 mL/min/1.73 m² (coefficient, –36.96, 95 percent CI, –41.62 to –32.30; p<0.001) vs ≥90 mL/min/1.73 m².

Notably, GEE found no significant difference among the three study medications. Compared to the TAF referent, for example, neither TDF (coefficient, –0.21, 95 percent CI, –4.92 to 4.51; p=0.93) nor ETV (coefficient, 1.85, 95 percent CI, –1.89 to 5.58; p=0.33) was able to demonstrate significant superiority.

“LT recipients treated with TAF maintained comparable eGFR as those on TDF by 24-month follow-up despite having poorer pretreatment renal function, older age, and higher rates of hypertension,” the researchers said. “Future studies with larger samples and extended follow-up times are needed to evaluate the long-term renal effects of TAF vs TDF vs ETV.”