Relative importance of weight gain among cardiometabolic risk factors in the development of metabolic dysfunction-associated steatotic liver disease: An observational study using large-scale health examination data

Objective Among cardiometabolic risk factors (CMRs), the relative contribution of obesity-related indices, particularly the body mass index (BMI) and waist circumference, to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. We assessed the impact of these indices on incident MASLD compared with other CMRs and determined the threshold of weight gain associated with an increased risk. Methods This retrospective cohort study included 7,687 individuals without steatotic liver disease at baseline who underwent health screening. The baseline risk factors and 5-year weight changes were assessed to evaluate their associations with incident MASLD. The participants were stratified according to the presence or absence of CMRs. Results Multivariable logistic regression analyses showed that baseline obesity was the strongest factor associated with incident MASLD (odds ratio (OR), 2.75; 95% confidence intervals (CI), 2.33-3.24), followed by a history of weight gain of ≥10 kg since 20 years of age (OR, 2.23; 95% CI, 1.90-2.63). A dose-response relationship was observed between the 5-year weight gain and MASLD incidence. The risk of MASLD increased from a 3-5% weight gain in participants with baseline CMRs (OR = 2.39; 95% CI = 1.92-2.99), whereas a higher threshold of 7-10% was required in those without CMRs (OR = 3.92; 95% CI = 2.05-7.47). Conclusions Among CMRs, obesity-related indices were the most influential factors for incident MASLD. The threshold for weight gain differed according to the baseline CMR status, highlighting the importance of individualized weight management strategies. These findings provide clinically relevant thresholds for weight management in the prevention of MASLD.