DAY 1: Treatment with Resmetirom May Prevent Cognitive Decline in Patients with Metabolic Dysfunction-Associated Steatohepatitis

The benefit of resmetirom treatment may extend beyond liver fat reduction and a decrease in metabolic risk, as evidenced by an exploratory analysis that showed gains in cognitive function and quality of life for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), treated with this medication. The results were presented in a poster session at the 2025 Annual Scientific Meeting of the American College of Gastroenterology in Phoenix, Arizona.

“Patients with MASLD and MASH can experience subtle but meaningful deficits in attention, memory, and executive function, even before advanced fibrosis or cirrhosis,” said author Maria Stepanova, PhD, a member of the Global NASH Council. “These deficits may be reflecting the liver-brain axis along with metabolic or inflammatory mechanisms. These cognitive changes can significantly reduce health-related quality of life (HRQL), yet are often underrecognized and rarely captured by standard clinical or HRQL tools used in liver disease.”  

Stepanova and colleagues collected data from patients with MASLD or MASH enrolled in the MAESTRO clinical trials who had completed HRQL instruments at baseline and again at weeks 24 and 52 of treatment, and used the information to develop a surrogate instrument for self-reporting cognitive function. Questions were designed to ask patients about memory deficits, difficulty concentrating, confusion, and the duration of concentration deficits.

Half of the 2243 patients who had completed HRQL instruments in the MAESTRO trials had early MASH, while 42% had moderate-to-advanced MASH, and 8% had MASH cirrhosis. The self-reported cognitive function scores of patients with early MASH were significantly higher than those of patients with moderate-to-advanced MASH or cirrhosis. The data also showed that younger age, female sex, history of depression, clinically overt fatigue, and higher liver stiffness were independently associated with low self-reported scores of cognitive function.

During treatment with resmetirom, patients with early MASH who received placebo experienced a decrease in self-reported cognitive function domain scores, whereas no such decrease was observed in patients treated with either 80 mg or 100 mg of resmetirom. The changes in self-reported cognitive function scores were similar in patients with and without treatment response to resmetirom across all subgroups.

“Cognitive function self-report and worry scores in patients with MASH capture different aspects of health-related quality of life that can be affected by patient characteristics and treatment,” Stepanova concluded. “The cognitive function self-report domain score offers a practical means of capturing patient-perceived deficits in cognition in both research settings and clinical care.”