▎药明康德团队
代谢功能障碍相关脂肪性肝病（MASLD）是一种对健康构成严重威胁的疾病，多达三分之一的患者会发展为进行性脂肪性肝炎和肝纤维化，这些状况最终可能导致肝硬化、肝细胞癌甚至死亡。近期发表于
JAMA期刊的一项2期临床研究中，研究人员将目光转向了阿司匹林这一经济有效的治疗方案，探究了低剂量阿司匹林在治疗MASLD中的潜在益处。这项初步研究的成果为改善该患者群体的治疗方法和疾病管理提供了新的希望。
既往的临床前研究表明，阿司匹林能逆转肝脂肪变性和炎症，并且能够降低肝纤维化和肝细胞癌的风险。对MASLD患者的观察性研究也提示，阿司匹林的使用与较低的肝病进展率和死亡率相关联。尽管有一项小型非随机研究显示，22名脂肪肝病患者在接受阿司匹林单独治疗或与氯吡格雷联合的抗血小板治疗6个月后，肝脂肪含量有所减少，但由于研究设计局限，阿司匹林治疗MASLD方面的确切疗效尚不明确，需要进一步研究。
基于这些初步发现，研究人员开展了一项2期随机临床试验，旨在评估低剂量阿司匹林（81 mg/天）相比于安慰剂在6个月内减少肝脂肪的效果。在这项研究中，MASLD患者随机分为两组，一组接受每天一次的低剂量阿司匹林治疗，为期六个月，而对照组则接受相应的安慰剂治疗。
本研究的主要终点是通过磁共振波谱（MRS）测量的从基线至第6个月时肝脂肪分数的平均绝对变化。
此外，研究中预先指定的关键次要终点还包括：通过MRS测量的肝脂肪分数在6个月内的相对（百分比）变化、肝脂肪分数至少减少30个百分点、以及通过磁共振成像-质子密度脂肪分数（MRI-PDFF）测量的肝脂肪含量的绝对和相对变化。
图片来源：123RF
研究结果显示，与安慰剂组相比，服用低剂量阿司匹林的患者在6个月的治疗期内，其绝对和相对肝脂肪分数均显著降低，表明阿司匹林有效减少了肝脂肪积聚。具体来说，阿司匹林组的平均绝对肝脂肪分数较基线降低了10.3%，而安慰剂组的肝脂肪分数则略有上升。除此之外，阿司匹林还显著降低了丙氨酸氨基转移酶（ALT）水平、天冬氨酸氨基转移酶（AST）水平，并减轻了肝脏的炎症和纤维化。值得注意的是，两组在平均绝对体重变化以及试验期间体重减少≥3%的比例方面，并未显示出显著差异。
在本项研究中，低剂量阿司匹林展现了良好的安全性和耐受性，未观察到与药物相关的严重不良事件或出血事件。然而，在文中指出，鉴于治疗期较短，对于那些通常不满足常规阿司匹林使用标准的MASLD患者，其长期风险与益处仍需未来研究予以明确。
本研究的主要研究者Tracey G. Simon博士在接受STAT采访时提到，对于MASLD这类疾病，任何新的治疗手段都备受期待，哪怕是新批准的药物也可能仅适用于一小部分患者。阿司匹林作为一种价格低廉、广为人知的现有药物，其重复利用具有显著的吸引力，尤其是考虑到其安全性已经得到广泛认可。
图片来源：123RF
该研究也存在一些局限性。首先是其样本规模小（仅80名参与者），这使得在更大的患者群体中进行验证试验具有必要性。此外，阿司匹林对肝脏炎症的具体影响、其是否能够阻止疾病进展至更严重阶段（如肝硬化）还需进一步研究；还有一些基本问题亟待解答，例如哪些MASLD患者最适合接受阿司匹林治疗。考虑到晚期肝病患者常有出血和凝血问题，且血小板计数较低，阿司匹林的使用在这一群体中需慎重考虑。最后，还需要进行更多研究以确定针对MASLD患者的最佳阿司匹林治疗方案，包括开始服药时间、剂量及疗程长度。
值得一提的是，在进一步分析中，研究人员还研究了肝脏脂肪相对减少至少30个百分点的情况。结果发现，大约43%的阿司匹林组人员达到了这一临界点，而安慰剂组只有12.5%。这一发现为后续更大规模的临床研究提供了基础，有助于进一步验证阿司匹林的治疗效果。
让我们我们期待未来的相关研究能够为MASLD患者提供更多的治疗选择，并为临床实践带来变革。
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rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root:not([data-weui-theme=light]),body:not(.pages_skin_pc) body:not([data-weui-theme=light]){--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .8);--weui-FG-HALF: rgba(255, 255, 255, .6);--weui-FG-1: rgba(255, 255, 255, .5);--weui-FG-2: rgba(255, 255, 255, .3);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: #ff6146;--weui-ORANGE: #c87d2f;--weui-YELLOW: #cc9c00;--weui-GREEN: #74a800;--weui-LIGHTGREEN: #3eb575;--weui-BRAND: #07c160;--weui-BLUE: #10aeff;--weui-INDIGO: #1196ff;--weui-PURPLE: #8183ff;--weui-WHITE: rgba(255, 255, 255, .8);--weui-LINK: #7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root:not([data-weui-theme=light]),body:not(.pages_skin_pc) 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#fff;--weui-LINK: #576b95;--weui-TEXTGREEN: #06ae56;--weui-FG: #000;--weui-BG: #fff;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: #fa9d3b;--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: #06ae56;--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: #10aeff;--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(0, 0, 0, .5);--weui-TAG-BACKGROUND-BLACK: rgba(0, 0, 0, .05)}.wx-root,body{--weui-BTN-ACTIVE-MASK: rgba(0, 0, 0, .1)}.wx-root,body{--weui-BTN-DEFAULT-ACTIVE-BG: #e6e6e6}.wx-root,body{--weui-DIALOG-LINE-COLOR: rgba(0, 0, 0, .1)}.wx-root,body{--weui-BG-COLOR-ACTIVE: #ececec}@media(prefers-color-scheme:dark){.wx-root:not([data-weui-theme=light]),body:not([data-weui-theme=light]){--weui-BTN-ACTIVE-MASK: rgba(255, 255, 255, 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59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media(prefers-color-scheme:dark){.wx-root:not([data-weui-theme=light]),body:not([data-weui-theme=light]){--discussInput-BG: rgba(255, 255, 255, .03)}}@media(prefers-color-scheme:dark){.wx-root:not([data-weui-theme=light]),body:not([data-weui-theme=light]){--nickName-FG: #959595}}@media(prefers-color-scheme:dark){.wx-root:not([data-weui-theme=light]),body:not([data-weui-theme=light]){--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .8);--weui-FG-HALF: rgba(255, 255, 255, .6);--weui-FG-1: rgba(255, 255, 255, .5);--weui-FG-2: rgba(255, 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