Tenofovir amibufenamide

Chronic hepatitis B (CHB) remains a significant global health challenge, and effective antiviral therapies are essential for long-term management. This study aimed to evaluate the real-world effectiveness and safety of tenofovir amibufenamide (TMF) in a cohort of patients with chronic hepatitis B (CHB).

In this multicenter, prospective, real-world cohort study, 194 CHB patients were recruited from four hospitals between August 2021 and August 2022. Patients were divided into treatment-naïve (TN, n = 123) and treatment-experienced (TE, n = 71) groups. The TN group was further subdivided into TMF (n = 63) and tenofovir disoproxil fumarate (TDF, n = 60) subgroups. In the TE group, patients transitioned from prior antiviral therapies (entecavir or TDF) to TMF after meeting criteria for poor virological response or safety concerns. Treatment response was evaluated in terms of virological effectiveness and alanine transaminase normalization rates. Virological response (VR), ALT normalization rates, renal function markers, and lipid profiles were monitored.

In the TN cohort, VR rates at 24 and 48 weeks were 42.86% and 90.48% for TMF, and 60.00% and 83.33% for TDF. ALT normalization rates at 24 and 48 weeks for TMF were 56.82% and 70.45% (according to AASLD 2018 standards). In the TE group, VR rates at 24 and 48 weeks were 83.1% and 91.55%, respectively. ALT normalization rates were 86.67% and 93.33% (local standards), and 66.67% and 76.67% (AASLD 2018 standards) (z = -2.822, P = 0.005). Additionally, TMF showed improved renal safety over TDF, with no significant differences in lipid concentrations.

TMF is comparable to TDF in terms of CHB treatment effectiveness, with better renal safety and no impact on lipid levels. In TE patients, transitioning to TMF therapy does not affect antiviral treatment outcomes.

Objective: To compare the effectiveness and safety profile of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF), especially the effects on lipid metabolism in the treatment of chronic hepatitis B. Methods: A retrospective study was conducted on the virological response rate, biochemical response rate, renal function indicators, and lipid metabolism status of 159 cases with chronic hepatitis B (72 cases with TMF and 87 cases with TAF) after 48 weeks of antiviral treatment. The effects of the two drugs on lipid metabolism were further explored through cell and animal experiments. Results: There were no statistically significant differences in baseline age, gender ratio, treatment-naïve and treatment-experienced proportions, hepatitis B virus (HBV) DNA and aminotransferase levels, renal function indicators, and serum lipid levels between the two groups. The levels of HBV DNA and transaminase were significantly reduced after 48 weeks of treatment in both groups. However, there were no statistically significant differences in virological response (84.2% vs. 75.8%, χ²=0.733, P=0.392) and biochemical response rate (86.1% vs. 85.1%, χ²=0.035, P=0.851) between the two groups. There was no significant change in the renal function index levels before and after treatment between the two groups of patients. Triglyceride [TG, 1.30 (0.93, 1.81) mmol/L vs. 1.30 (0.82, 1.84) mmol/L, Z=-0.196, P=0.844], total cholesterol [TC, 4.53 (3.91, 5.15) mmol/L vs. 4.55 (3.88, 5.24) mmol/L, Z=-1.131, P=0.258], high-density lipoprotein [HDL-C, 1.04 (0.90, 1.3) mmol/L vs. 1.08 (0.94, 1.30) mmol/L, Z=-0.811, P=0.417], low-density lipoprotein [LDL-C, 2.68 (2.04, 3.29) mmol/L vs. 2.57 (1.99, 3.49) mmol/L, Z=-1.716, P=0.086] and the ratio of total cholesterol to high-density lipoprotein [TC/HDL-C, 4.52 (3.10, 5.23) vs. 4.30 (3.27, 5.01), Z=-0.410, P=0.682] had not statistically significant differences in the TMF group before and after treatment. TG [1.24(0.95, 1.98) mmol/L vs. 1.42(1.09, 2.21) mmol/L, Z=-2.895, P=0.004], TC [4.44(3.74, 5.26) mmol/L vs. 4.68(4.07), 5.46) mmol/L, Z=-2.825, P=0.005], low-density lipoprotein (LDL-C) [2.74 (2.05, 3.58) mmol/L vs. 2.87 (2.34, 3.50) mmol/L, Z=-2.419, P=0.016] , and TC/HDL-C [3.89(3.13, 4.82) vs. 4.39(3.70, 5.40), Z=-4.478, P<0.001] levels were increased after TAF treatment, while HDL-C levels were decreased [1.19 (0.98, 1.35) mmol/L vs. 1.04 (0.90, 1.33) mmol/L, Z=-3.070, P=0.002]. The absolute values comparison changes had no statistically significant differences in TG [-0.04(-0.37, 0.46) mmol/L and 0.18 (-0.14, 0.46) mmol/L, Z=-1.853, P=0.064], TC [0.06(-0.38, 0.63) mmol/L vs. 0.23(-0.21, 0.65) mmol/L, Z=-1.010, P=0.312] and LDL-C level [-0.19(-0.33, 0.18) mmol/L vs. 0.18 (-0.13, 0.58) mmol/L, Z=-0.523, P=0.601] before and after treatment between the two groups of patients. The TMF group had higher HDL-C [0.06 (-0.16, 1.84) mmol/L vs. -0.12 (-0.26,0.04) mmol/L, Z=-2.890, P=0.004], but lower TC/HDL-C [-0.04(-0.67, 0.44) vs. 0.40(-0.14, 1.33), Z=-3.959, P<0.001] than the TAF group. HepG2 cells were interfered with 10 μg/ml TMF and TAF for 72 hours, respectively. Microscopic examination revealed that in the TMF group [12 196 (10 740, 14 345) vs. 4 029 (3 086, 5 425) cells, Z=-4.815, P<0.001] and TAF group [12 484 (11 176, 15 824) vs. 4 029 (3 086, 5 425), Z=-4.815, P<0.001], the number of intracellular lipid droplets was higher than that in the control group after Oil Red O staining, but the difference between the two groups was not statistically significant. Ten-week-old C57/BL6J male mice were given 3.8 mg/kg TMF or TAF by continuous gavage for 12 weeks. The liver tissue was stained with Oil Red O. The number of lipid droplets was higher in the liver tissue of mice in the TAF group than that of the control group [30 647 (28 050, 34 821) and 27 614 (25 214, 29 176), Z=-2.529, P=0.011], while the difference between the TMF group and control group was not statistically significant. The serum TG levels were higher in the TAF group mice [1.17 (1.11, 1.19) μmol/L vs. 1.06 (1.04, 1.09) μmol/L, Z=-2.060, P=0.039], TC [2.58 (2.55, 2.80) μmol/L L vs. 2.33 (2.18, 2.54) μmol/L, Z=-2.084, P=0.037] than those of the control group after drug administration, while HDL-C levels were lower than those of the control group [1.14 (1.13, 1.16) μmol/L vs. 1.29 (1.28, 1.32) μmol/L, Z=-2.313, P=0.021] and TMF group [1.14 (1.13, 1.16) μmol/L vs. 1.30 (1.28, 1.38) μmol/L, Z=-2.795, P=0.005]. However, there was no statistically significant difference in TG, TC, and HDL-C levels between the TMF and the control group. Conclusion: Both TMF and TAF can effectively inhibit HBV replication and promote liver function recovery, with no significant impact on renal function. However, TAF may generate an adverse effect on lipid metabolism in the body, while TMF has no obvious effect.