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Non-invasive biomarkers for the assessment of treatment response are highly needed in the clinical setting for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This study evaluates the role of Controlled Attenuation Parameter (CAP) by Vibration-Controlled Transient Elastography and PNPLA3 gene variants for the assessment of weight loss and BMI reduction in MASLD patients undergoing a 6-month dietary intervention. 94 MASLD patients were randomly assigned to 3 arms: Mediterranean Diet (MD), Low-Charb Diet (LCD), and Control Diet (CD). Inclusion criteria were BMI 26-35 kg/m², CAP≥248 dB/m, Liver Stiffness Measurement (LSM)<12 kPa. Primary endpoints was ≥7% weight loss. Clinical/biochemical parameters and VCTE were assessment at baseline and after 6 months. Median age was 50.5 [IQR 43.0-61.0] years and 71.3% was male. Type 2 diabetes (T2D) was present in 17% of cases and PNPLA3 GG was present in 19.1% of cases. After 6 months, 28.7% of patients achieved ≥7% weight loss, with the highest proportion in LCD group (36.2%). In all patients achieving weight loss, CAP significantly decreased (from median 294 to median 246 dB/m, p<0.0001), as compared to CAP changes that were observed in those who did not achieve weight loss (inter-group p-value=0.001). Delta CAP values were higher in LCD group (p=0.040). A stepwise increase in the delta CAP values was observed across incremental weight loss categories (<5%, 5-10%,>10%) (p=0.02). In patients achieving≥7% weight loss, delta CAP values were higher in patients with CC/CG genotype (p=0.0004), as compared to GG carriers (p=0.79). In patients with MASLD undergoing lifestyle intervention, weight loss≥7% was associated with significant decreases in CAP values. PNPLA3 genotyping may be useful for further patient stratification. [ABSTRACT FROM AUTHOR]