本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.1215

摘要内容如下：

重要性

阿司匹林可减轻代谢功能障碍相关性脂肪变性肝病（MASLD）的严重程度，降低MASLD患者终末期肝病和肝细胞癌的发生率。然而，阿司匹林对MASLD的影响尚不清楚。

目的

测试与安慰剂相比，低剂量阿司匹林是否能降低成人MASLD患者的肝脏脂肪含量。

设计、设置和参与者

这项为期6个月、2期、随机、双盲、安慰剂对照的临床试验在马萨诸塞州波士顿的一家医院进行。参与者年龄为18至70岁，已建立MASLD，但无肝硬化。招募时间为2019年8月20日至2022年7月19日，最后随访时间为2023年2月23日。

干预措施

参与者随机（1:1）接受每日一次的阿司匹林，81毫克（n=40）或相同的安慰剂（n=40），为期6个月。

主要成果和措施

主要终点是6个月随访时通过质子磁共振波谱（Mrs）测量的肝脏脂肪含量的平均绝对变化。4个关键的次要结果包括通过Mrs测量的肝脏脂肪含量的平均百分比变化，实现肝脏脂肪至少减少30%的比例，以及通过磁共振成像质子密度脂肪分数（MRI-PDFF）测量的肝脏脂肪含量的平均绝对和相对减少。根据相应结果的基线值调整的分析。未预先规定研究结果的最小临床重要差异。

结果

在80名随机参与者中（平均年龄48岁；44名[55%]妇女；平均肝脏脂肪含量，35%[表明中度脂肪变性]），71人（89%）完成了6个月的随访。阿司匹林组肝脏脂肪含量的平均绝对变化为-6.6%，安慰剂组为3.6%（差异，-10.2%[95%CI，-27.7%至-2.6%]；P=.009）。与安慰剂相比，阿司匹林治疗显著降低了相对肝脏脂肪含量（-8.8比30.0个百分点；平均差，-38.8个百分点[95%CI，-66.7至-10.8]；P=.007），增加了肝脏脂肪相对减少30%或更多的患者比例（42.5%vs 12.5%；平均差异，30.0%[95%CI，11.6%至48.4%]；P=.006），通过MRI-PDFF降低肝脏脂肪绝对含量（-2.7%vs 0.9%；平均差，-3.7%[95%CI，-6.1%至-1.2%]；P=.004]），并通过MRI-PDFF降低相对肝脏脂肪含量（-11.7比15.7个百分点；平均差，-27.3个百分点[95%CI，-45.2至-9.4]；P=.003）。每组中有13名参与者（32.5%）出现不良事件，最常见的是上呼吸器官感染（每组10.0%）或关节痛（阿司匹林组5.0%，安慰剂组7.5%）。一名随机接受阿司匹林治疗的参与者（2.5%）出现了药物相关的胃灼热。

结论和相关性

在这项MASLD患者的初步随机临床试验中，与安慰剂相比，6个月的每日低剂量阿司匹林显著降低了肝脏脂肪量。有必要在更大的样本量中进行进一步的研究，以证实这些发现。

试用注册

ClinicalTrials.gov标识符：NCT04031729。

英文原文如下：

Abstracts

Importance  Aspirin may reduce severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown.

Objective  To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD.

Design, Setting, and Participants  This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023.

Interventions  Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months.

Main Outcomes and Measures  The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified.

Results  Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was -6.6% with aspirin vs 3.6% with placebo (difference, -10.2% [95% CI, -27.7% to -2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (-8.8 vs 30.0 percentage points; mean difference, -38.8 percentage points [95% CI, -66.7 to -10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (-2.7% vs 0.9%; mean difference, -3.7% [95% CI, -6.1% to -1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (-11.7 vs 15.7 percentage points; mean difference, -27.3 percentage points [95% CI, -45.2 to -9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn.

Conclusions and Relevance  In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings.

Trial Registration  ClinicalTrials.gov Identifier: NCT04031729.

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