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.
目的： 比较艾米替诺福韦（TMF）与富马酸丙酚替诺福韦（TAF）治疗慢性乙型肝炎的有效性与安全性，尤其是对脂质代谢的影响。 方法： 回顾性研究159例（TMF组72例，TAF组87例）慢性乙型肝炎患者抗病毒治疗48周后的病毒学应答率、生物化学应答率、肾功能指标和脂质代谢情况。并通过细胞实验和动物实验进一步探索两种药物对脂质代谢的影响。组间数据比较采用秩和检验和χ2检验。 结果： 两组患者基线年龄、性别比例、初治和经治比例、乙型肝炎病毒（HBV）DNA和转氨酶水平、肾功能指标及血脂指标水平的差异均无统计学意义。治疗48周后，两组患者HBV DNA和转氨酶水平均显著下降，病毒学应答率（84.2%与75.8%，χ2=0.733，P=0.392）和生物化学应答率（86.1%与85.1%，χ2=0.035，P=0.851）两组间的差异无统计学意义。两组患者治疗前后肾功能指标水平无明显变化。TMF组治疗前后甘油三酯［TG；1.30（0.93，1.81）mmol/L与1.30（0.82，1.84）mmol/L，Z=-0.196，P=0.844］、总胆固醇［TC；4.53（3.91，5.15）mmol/L与4.55（3.88，5.24）mmol/L，Z=-1.131，P=0.258］、高密度脂蛋白胆固醇［HDL-C；1.04（0.90，1.30）mmol/L与1.08（0.94，1.30）mmol/L，Z=-0.811，P=0.417］、低密度脂蛋白胆固醇［LDL-C；2.68（2.04，3.29）mmol/L与2.57（1.99，3.49）mmol/L，Z=-1.716，P=0.086］和TC/HDL-C［4.52（3.10，5.23）与4.30（3.27，5.01），Z=-0.410，P=0.682］的差异均无统计学意义。TAF治疗后TG［1.24（0.95，1.98）mmol/L与1.42（1.09，2.21）mmol/L，Z=-2.895，P=0.004］、TC［4.44（3.74，5.26）mmol/L与4.68（4.07，5.46）mmol/L，Z=-2.825，P=0.005］、LDL-C［2.74（2.05，3.58）mmol/L与2.87（2.34，3.50）mmol/L，Z=-2.419，P=0.016］水平升高，TC/HDL-C也升高［3.89（3.13，4.82）与4.39（3.70，5.40），Z=-4.478，P<0.001］；HDL-C水平下降［1.19（0.98，1.35）mmol/L与1.04（0.90，1.33）mmol/L，Z=-3.070，P=0.002］。两组患者治疗前后变化的绝对值比较，TG［-0.04（-0.37，0.46）mmol/L与0.18（-0.14，0.46）mmol/L，Z=-1.853，P=0.064］、TC［0.06（-0.38，0.63）mmol/L与0.23（-0.21，0.65）mmol/L，Z=-1.010，P=0.312］和LDL-C水平［-0.19（-0.33，0.18）mmol/L与0.18（-0.13，0.58）mmol/L，Z=-0.523，P=0.601］差异无统计学意义，TMF组HDL-C较高［0.06（-0.16，1.84）mmol/L与-0.12（-0.26，0.04）mmol/L，Z=-2.890，P=0.004］，TC/HDL-C也低于TAF组［-0.04（-0.67，0.44）与0.40（-0.14，1.33），Z=-3.959，P<0.001］。分别使用10 μg/ml的TMF和TAF对HepG2细胞干预72 h，油红O染色后显微镜检发现，TMF组［12 196（10 740，14 345）个与4 029（3 086，5 425）个，Z=-4.815，P<0.001］和TAF组［12 484（11 176，15 824）个与4 029（3 086，5 425）个，Z=-4.815，P<0.001］的细胞内脂滴数量多于对照组，但两组间的差异无统计学意义。对10周龄C57/BL6J雄性小鼠分别给予3.8 mg/kg的TMF或TAF连续灌胃12周，肝组织油红O染色，TAF组小鼠肝组织脂滴数量多于对照组［30 647（28 050，34 821）个与27 614（25 214，29 176）个，Z=-2.529，P=0.011］，而TMF组与其对照组间的差异无统计学意义。给药后TAF组小鼠血清TG［1.17（1.11，1.19）μmol/L与1.06（1.04，1.09）μmol/L，Z=-2.060，P=0.039］、TC［2.58（2.55，2.80）μmol/L与2.33（2.18，2.54）μmol/L，Z=-2.084，P=0.037］水平均高于对照组、HDL-C水平低于其对照组［1.14（1.13，1.16）μmol/L与1.29（1.28，1.32）μmol/L，Z=-2.313，P=0.021］和TMF组［1.14（1.13，1.16）μmol/L与1.30（1.28，1.38）μmol/L，Z=-2.795，P=0.005］。TMF组TG、TC、HDL-C水平与其对照组间的差异无统计学意义。 结论： TMF和TAF均能有效抑制HBV复制，促进肝功能恢复，且都对肾功能无明显影响，但TAF可能对机体脂质代谢产生不利影响，而TMF则影响不明显。.