Revisiting the Obesity Paradox in Metabolic Dysfunction-associated Steatotic Liver Disease: Longitudinal Trajectory...

Area of Science:

• Hepatology
• Metabolic Diseases
• Epidemiology

Background:

• Obesity is a primary driver of metabolic dysfunction-associated steatotic liver disease (MASLD).
• Obese patients with MASLD paradoxically show better survival rates than non-obese individuals.
• The
• obesity-survival paradox
• in MASLD requires further investigation using longitudinal data.

Purpose of the Study:

• To investigate the
• obesity-survival paradox
• in MASLD.
• To analyze the association between Body Mass Index (BMI) trajectories and mortality risk in MASLD patients.

Main Methods:

• Analysis of three large population-based MASLD cohorts (NHANES III, NHANES 1999-2018, UK Biobank).
• Utilized multivariable-adjusted restricted cubic spline models to assess BMI-mortality dose-response relationships.
• Employed latent class trajectory modeling to identify distinct long-term BMI patterns.

Main Results:

• Obesity (BMI > 30) in mid-to-late adulthood or post-MASLD diagnosis correlated with reduced overall mortality.
• Higher early-adulthood BMI was associated with increased mortality.
• Persistent obesity and rapid BMI increase were linked to significantly higher mortality, while persistent non-obesity predicted lower risk.

Conclusions:

• The relationship between obesity and MASLD outcomes is heterogeneous, depending on the timing of obesity exposure.
• Long-term BMI trajectory analysis indicates that obesity does not confer a survival advantage in MASLD.
• Maintaining a non-obese status throughout adulthood is associated with lower overall mortality in MASLD.