Published online Jul 14, 2025. doi: 10.3748/wjg.v31.i26.109285
Revised: May 30, 2025
Accepted: June 23, 2025
Published online: July 14, 2025
Processing time: 65 Days and 22.2 Hours
Tenofovir amibufenamide (TMF) has shown antiviral efficacy comparable to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB), with improved renal and bone safety profiles. While TDF is recognized for its lipid-lowering properties, the long-term effects of TMF on lipid metabolism remain unclear.
To assess lipid changes and long-term safety of TMF in CHB, including outcomes after TDF-to-TMF switch over 144 weeks.
This retrospective analysis utilized data from a phase III randomized, double-blind trial involving 53 patients with CHB treated with either TMF 25 mg (n = 39) or TDF 300 mg (n = 14) once daily for 96 weeks. Following this blinded phase, all participants entered an open-label extension in which they received TMF until week 144. This design enabled assessment of both the comparative effects of TMF and TDF and the impact of switching from TDF to TMF, thereby reflecting real-world treatment scenarios. Virological, biochemical and imaging evaluations were performed throughout the study.
At week 96, both groups achieved comparable virological suppression and maintained stable hepatic and renal function. However, total cholesterol and low-density lipoprotein cholesterol levels were significantly higher in the TMF group compared to the TDF group (P = 0.012 and P = 0.040, respectively). TDF was associated with a transient increase in serum phosphate (P = 0.030). After switching to TMF, lipid profiles in the former TDF group gradually aligned with those of the continuous TMF group by week 144, with no lipid abnormalities observed in either group.
TMF provides sustained antiviral efficacy and maintains a favourable long-term lipid and renal safety profile. These findings support TMF as a viable first-line therapy and a switch option for CHB management in clinical practice.
Core Tip: This 144-week dual-phase study investigated the long-term lipid and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B patients. Through a randomized, double-blind comparison with tenofovir disoproxil fumarate (TDF) followed by a TDF-to-TMF switch, the trial revealed comparable antiviral efficacy, improved renal and bone safety, and a moderate elevation in lipid levels with TMF that stabilized after switch therapy. These findings support TMF as a viable first-line and sequential therapy option in real-world chronic hepatitis B management.