Weight change across adulthood in relation to ultrasound-defined metabolic dysfunction-associated steatotic liver...

Although obesity is a well-established risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the impact of long-term weight trajectories on MASLD risk remains unclear. We aimed to examine the association between weight change trajectories across adulthood and the risk of ultrasound-defined MASLD.

We analysed data from 4999 participants from the Healthy Happy Aging Community Cohort. Weight trajectories were assessed using body mass index (BMI) at age 25 years, ten years before baseline, one year before baseline, and at baseline. MASLD was defined as a median (MD) controlled attenuation parameter (CAP) of ≥274 dB/m and severe steatosis as a MD CAP of ≥302 dB/m via vibration-controlled transient elastography.

There were 2247 (44.9%) patients with MASLD, of whom 1468 (29.4%) had severe steatosis. Compared with stable normal weight, sustained obesity (BMI ≥ 30 kg/m² at all time points) demonstrated a strong association with MASLD risk (adjusted odds ratio (aOR) = 2.17; 95% confidence interval (CI) = 1.64-2.86), particularly for severe steatosis (aOR = 2.52; 95% CI = 1.74-3.66). The transition from non-obese to obese status was associated with a 2.5-fold increase in risk (aOR = 2.51; 95% CI = 1.81-3.48), with a more pronounced effect observed in men (P-interaction <0.05). Weight gain of ≥5 kg between ages 25-40 years showed particularly strong associations (aOR = 2.20; 95% CI = 1.70-2.86), while baseline severe obesity (BMI ≥ 35 kg/m²) remained the strongest independent predictor (aOR = 4.12; 95% CI = 2.70-6.29).

Long-term obesity and weight gain, especially in early adulthood, significantly increase MASLD risk. Sustained obesity and progression to obesity were key risk factors, with severe obesity showing the strongest association. Early weight management is crucial for MASLD prevention.