Aspirin for Metabolic Dysfunction–Associated Steatotic Liver Disease Without Cirrhosis

Abstract

ImportanceAspirin 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.ObjectiveTo test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD.Design, Setting, and ParticipantsThis 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.InterventionsParticipants 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 MeasuresThe 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.ResultsAmong 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT04031729

Low-Dose Aspirin and Hepatic Fat Quantity in Patients With MASLD

“…Given the small sample size of the recent study, further investigation in larger cohorts is warranted to confirm these findings. In addition, incorporation of cost-effective serum biomarkers of steatosis could potentially increase sample sizes and enhance the robustness of study outcomes.…”

“…To the Editor We have some comments about the recent article that reported the efficacy of low-dose aspirin in reducing hepatic fat quantity in patients with metabolic dysfunction–associated steatotic liver disease (MASLD).…”

“…The primary end point of the study was the mean absolute change in hepatic fat fraction, measured by single-voxel breath-hold 1H–magnetic resonance spectroscopy (1H-MRS). While magnetic resonance imaging is the criterion standard for quantitative measurement of liver fat, we suggest considering the inclusion of serum biomarkers of steatosis, such as the SteatoTest and the Fatty Liver Index (FLI), in future studies.…”

Low-Dose Aspirin and Hepatic Fat Quantity in Patients With MASLD

“…To the Editor A recent clinical trial of the effect of low-dose aspirin on MASLD lasted 6 months and demonstrated that daily low-dose aspirin decreased hepatic fat content compared with placebo. However, I have some concerns about the applicability and long-term consequences of these results.…”

Low-Dose Aspirin and Hepatic Fat Quantity in Patients With MASLD

“…To the Editor Although a recent study about the therapeutic potential of aspirin in managing MASLD without cirrhosis provided valuable insights, we have several concerns about the study’s design and interpretation of results.…”