New treatment strategy for MASLD

By Katie Robinson | Fact-checked by Barbara Bekiesz
Published May 8, 2024

Key Takeaways

  • Six months’ use of daily low-dose aspirin reduced the liver fat content in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis, according to a phase 2 placebo-controlled trial.

  • Aspirin use also improved several markers of liver health associated with inflammation and fibrosis.

  • While results are encouraging, larger studies are needed to confirm the preliminary findings.

Patients with MASLD without cirrhosis who took daily low-dose aspirin for 6 months achieved a 10% reduction in their liver fat content compared with those who took placebo, according to a study by Massachusetts General Hospital investigators.[]

The study, published in JAMA, also found that low-dose aspirin use improved several markers of liver health associated with inflammation and fibrosis.

Aspirin’s potential

MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), affects up to a third of US adults. Patients with this most common chronic liver disease present with increased liver fat—often due to type 2 diabetes and obesity—that poses serious health risks.

However, based on the study findings, senior author Andrew T. Chan, MD, MPH, explained in a Mass General press release that “aspirin represents an attractive potential low-cost option to prevent progression to cirrhosis or liver cancer, the most feared complications of MASLD.”[]

Aspirin has shown hepatic anti-inflammatory effects in murine models by inhibiting cycloxygenase-2 and platelet-derived growth factor signaling. In cross-sectional studies of patients with NAFLD, the use of aspirin was associated with a reduced prevalence of liver steatosis and measures of fibrosis.

A previous prospective study by the Mass General researchers found that daily aspirin use was associated with less severe histologic features of NAFLD and non-alcoholic steatohepatitis, along with a lower risk of progression to advanced liver fibrosis.[]

In their latest phase 2 randomized, placebo-controlled trial, the researchers examined whether low-dose aspirin reduced liver fat content in adults with MASLD.

Between August 20, 2019, and July 19, 2022, the study enrolled 80 participants with MASLD without cirrhosis. The participants’ mean age was 48 years, 55% were women, and their mean hepatic fat content was 35%, indicating moderate steatosis. They were randomized (1:1) to receive either once-daily aspirin (81 mg) or placebo for 6 months. At the final follow-up on February 23, 2023, the researchers reported that 89% of the participants completed the 6-month follow-up. 

The primary endpoint—the mean absolute change in liver fat content measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up—was met.

The aspirin-treated patients had a 6.6% reduction in liver fat content, whereas the placebo group had a 3.6% increase, representing a 10.2% reduction in liver fat content with low-dose aspirin vs placebo.

Markers of liver health

The four key secondary outcomes were also met: (1) the mean change in liver fat content measured by MRS (aspirin reduced this by 38.8% vs placebo); (2) the proportion of patients achieving at least a 30% relative reduction in liver fat (aspirin increased this by 30%); and the mean absolute (3) and relative (4) reductions in hepatic fat content, both measured by MRI-PDFF (aspirin reduced these by 3.7% and 27.3%, respectively).

Lead author and principal investigator Tracey G. Simon, MD, MPH, summarized the study results in the press release: “Multiple non-invasive blood and imaging-based tests for liver fat, inflammation, and fibrosis all showed a similar direction of benefit that favored aspirin treatment. Together, these data support the potential for aspirin to provide benefits for patients with MASLD.”


During the study, low-dose aspirin was found to be safe and well-tolerated, although one participant in the aspirin group experienced drug-related heartburn. Overall adverse events occurred in 32.5% of each study group. Specifically, 10% of each group experienced upper respiratory tract infections, while arthralgias occurred in 5% of the aspirin group and 7.5% of the placebo group.

The researchers recommend further study with a larger sample size to determine whether continued aspirin use can reduce the long-term health complication risk associated with MASLD.

What this means for you

While larger studies are needed, this preliminary clinical trial showed that 6 months of daily low-dose aspirin use reduced the liver fat content in patients with MASLD without cirrhosis. Aspirin use also improved several markers of liver health associated with inflammation and fibrosis. The low-dose aspirin was well tolerated.

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