Aspirin reduces liver fat, improves markers of inflammation, fibrosis

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) – previously called nonalcoholic fatty liver disease (NAFLD) – but without cirrhosis, who were treated with daily low-dose aspirin, had significant reductions in liver fat for 6 months in a new trial.

“In MASLD without cirrhosis, aspirin given at 81 mL daily, led to a reduction in liver fat and improved markers of hepatic inflammation and fibrosis,’’ said study author Dr Robert Wilechansky from the Massachusetts General Hospital in Boston, Massachusetts, US at the Liver Meeting 2023.

He added that low-dose aspirin was safe and well tolerated, “but we would like to see larger, longer-term clinical trials to test the efficacy of aspirin for improving histology and preventing adverse outcomes in MASLD.’’  

Currently, they have no plans to test aspirin on a full dose. “Given the risk profile of the patients, a lower dose is preferable.”

Why aspirin

MASLD is a chronic, progressive disease with substantial morbidity and mortality. Currently, there are no approved therapies for MASLD in the US.

Observational studies have linked aspirin use with reduced prevalence and progression of MASLD. However, the efficacy and safety of aspirin for reducing hepatic steatosis, inflammation, and fibrosis in patients with MASLD remain unknown.

Wilechansky and colleagues investigated whether aspirin, with its anti-inflammatory properties, could be an effective treatment for MASLD. “If there is a reduction in inflammation, we may also see some reduction in steatohepatitis,” he said.

Aspirin or placebo for 6 months

Eighty adults with MASLD were randomly assigned to aspirin 81 mg once daily or placebo for 6 months. [The Liver Meeting 2023, abstract 144]

Excluded were patients with baseline cirrhosis or other liver disease, heavy drinkers, and those who had used aspirin within 6 months. Also excluded were those who used other antiplatelet or anticoagulant agents, as were patients with severe renal or cardiovascular disease, active cancer, pregnant, were breastfeeding, had thrombocytopenia, or undergone bariatric surgery in the past 2 years.

At baseline, 36.3 percent of all patients had F2–F3 fibrosis (moderate to severe scarring), as determined by vibration-controlled transient elastography (VCTE). Of 44 patients who had previously undergone liver biopsy, 37 (84.1 percent) were confirmed to have steatohepatitis.

Change in HFF

At 6 months, the absolute change in the primary endpoint of hepatic fat fraction (HFF) from baseline was a decline of 6.1 percent for patients treated with aspirin vs a 4.2 percent increase for those on placebo (p=0.009).

The relative change in HFF,  which was the secondary endpoint, was -59.2 percent for aspirin vs placebo (p=0.003).

Interestingly, aspirin was associated with a 30-percent relative reduction in HFF among 16 of the 40 patients treated with the drug.

Aspirin was also significantly better than placebo for the secondary endpoints of absolute change in hepatic fat by MRI proton-density fat fraction (MRI-PDFF) and the relative change in hepatic fat by MRI-PDFF (p=0.018 and p=0.009, respectively).

Likewise, aspirin use was associated with significantly greater reductions in liver transaminase levels and liver stiffness by VCTE.

There was one case of heartburn with aspirin, which led to discontinuation.

Session co-moderator Dr Mary McCarthy Rinella from the University of Chicago Pritzker School of Medicine, Chicago, Illinois, US said the 4 percent increase in liver fat with a placebo is “quite a lot.”

To this, Wilechansky commented: “There were a few outliers in the placebo group who experienced significant weight gain during the study, including one patient who gained 15 kg over 6 months.”

Most of the increase in hepatic fat among placebo recipients could be among this group, he added. However, when those patients were excluded from the adjusted analysis, the difference between aspirin and placebo became smaller but still significant, said Wilechansky.