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Updated: Apr 10, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
Self-Reported Cognitive Function in Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic
Zobair M Younossi1,2, Fatema Nader1, Dominic Labriola3
1The Global NASH/MASH Council, Washington, DC, United States.
Background:
Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) may experience cognitive impairment that negatively impacts their health-related quality of life (HRQL).
Aim:
To develop and evaluate a self-reported surrogate measure of cognitive function in MASLD, its associations with baseline clinical characteristics, and changes during treatment with resmetirom.
Methods:
Patients with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) enrolled in resmetirom clinical trials (MAESTRO-NAFLD, MAESTRO-NASH) who had completed HRQL instruments (LDQoL and CLDQ-NAFLD) at baseline, week 24 and week 52 of treatment. Using patients' data from both HRQL instruments, a Cognitive Function Self-Report score was developed.
Results:
There were 2243 patients enrolled in the clinical trials of resmetirom (50% early MASH, 42% F2-F3, 8% MASH cirrhosis). Exploratory factor analysis was performed, and the distribution of factor loadings suggested 5 items for the new Cognitive Function Self-Report score. Younger age, female sex, history of depression, clinically overt fatigue, and higher liver stiffness were independently associated with low Cognitive Function Self-Report scores (all P < 0.05). In turn, the Cognitive Function Self-Report score was strongly associated with the overall HRQL (all P < 0.0001). During treatment with resmetirom, early MASH patients receiving placebo experienced a decrease in Cognitive Function Self-Report score: mean (95% CI) change from baseline to week 24: -3.0 (-4.9 to -1.0), from baseline to week 52-2.7 (-4.7 to -0.6); no similar decrease was observed in patients treated with 80 mg or 100 mg of resmetirom (all P > 0.05). Patients who experienced improvement in their HRQL scores had Cognitive Function Self-Report scores improvement (P < 0.0001).
Conclusions:
The Cognitive Function Self-Report score offers a means of capturing patient-perceived deficits in cognition in both research and clinical care.
Clinical Trials Number:
MAESTRO-NAFLD-1, NCT04197479.
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