A recent randomized, phase 2 study by Gane, E.J. and colleagues presented at the American Association for the Study of Liver Diseases (AASLD): The Liver Meeting 2021 demonstrated the high long-term efficacy and safety of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) antiviral prophylaxis in post-orthotopic liver transplant (OLT) patients with chronic hepatitis B virus (HBV) infection.¹ The renal- and bone-protecting effects on patients with TAF were shown to be more profound than those with TDF.¹

In 2019, the World Health Organization (WHO) estimated that 820,000 deaths were caused by HBV, primarily from cirrhosis and hepatocellular carcinoma.² Individuals with HBV-related cirrhosis or HCC may be eligible to receive OLT, if available.³ Upon liver transplantation, antiviral therapy is needed to prevent graft hepatitis, which could result in subsequent graft loss.³ Besides, transplantation of nonrenal organs, such as the liver, is frequently complicated by chronic kidney disease (CKD).⁴

According to the 2018 AASLD Hepatitis B Guideline, TAF is the preferred treatment of chronic hepatitis B (CHB) along with TDF.⁵ Nonetheless, TDF has been associated with increased risks of renal toxicity and/or bone mineral density (BMD) reduction.⁶ In contrast, TAF, which was originally developed for reducing the negative impact of the drug on proximal renal function, has been shown to have a non-inferior antiviral activity to TDF among CHB patients with improved renal and bone safety, owing to the lower concentration of tenofovir achieved by TAF in the circulation.⁶

A life-long antiviral therapy is recommended for CHB patients who have undergone OLT for preventing potential graft loss. Given the risk of CKD on the liver graft and the renal-protecting effect of TAF in CHB patients, adopting TAF as the long-term prophylactic treatment in post-OLT patients could be more beneficial over TDF. However, the clinical efficacy and safety of TAF over TDF in these patients have yet to be evaluated and remain unknown.

This study was an open-label, phase 2 study with 1:1 randomization which aimed to evaluate the long-term safety and efficacy of TAF vs. TDF antiviral prophylaxis in post-OLT patients.¹ A total of 51 patients with a pretransplant diagnosis of HBV were enrolled.¹ In the randomized phase, 26 patients were initiated with TAF 25mg once daily (QD), and 25 participants continued TDF-containing treatment for 48 weeks.¹ In the open-label extension (OLE) phase, all patients were converted to TAF 25mg QD through week 192.¹

Results showed that both treatments were equally efficacious.¹ All enrolled patients achieved sustained viral suppression, defined as HBV deoxyribonucleic acid (DNA) <20IU/mL, through week 192.¹ In terms of safety, TAF and TDF were well tolerated in both the randomized phase and the OLE phase.¹ No grade 3-4 adverse events (AEs) or serious AEs related to the drugs were reported.¹

The renal function of the participants was assessed by the changes in the estimated glomerular filtration rate (eGFR) and the renal proximal tubular markers (i.e., retinol-binding protein and β2-microglobulin).¹ The TAF arm was shown to have an improved eGFR from the start of the study, which remained stable through week 192, whereas the eGFR in patients treated with TDF was not improved in the randomized phase and remained stable through week 192 (the OLE phase), despite the switch of treatment to TAF at week 48.¹ TAF was also shown to have a more profound reduction in the renal markers compared with TDF in the randomized phase, implying a greater renal-protecting effect with TAF.¹ When TDF was switched to TAF from week 48, the changes in the renal markers were similar at week 192 in both groups.¹

Furthermore, the effect of TAF and TDF on bone was evaluated by the BMD changes.¹ Patients treated with TAF showed improvements in hip and spine BMD throughout the study. However, BMD deteriorations were seen in patients treated with TDF at week 48. When the antiviral treatment was switched to TAF at week 48, improvements in BMDs were observed in the TDF group at week 192. In a subgroup analysis, patients in the TDF group with the baseline eGFR <50mL/min/1.73m² showed greater deterioration in BMD vs. those with the baseline eGFR ≥50mL/min/1.73m².¹ When the therapy was switched to TAF, increases in BMD were observed in the TDF group, regardless of the baseline eGFR.¹

In conclusion, this study demonstrated the equally high long-term safety and efficacy of TAF and TDF in CHB patients who have received OLT. However, due to the more profound renal- and bone-protecting effects, TAF is a more preferred option for the long-term antiviral prophylaxis in this group of patients.