Weight-Loss Plateau during Lifestyle Intervention Predicts Treatment Response in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity

Abstract

Introduction: Whether the weight-loss plateau and its values differ in obesity with or without metabolic dysfunction-associated steatotic liver disease (MASLD) undergoing continuous lifestyle intervention remains unknown. We aimed to investigate this problem. Methods: This prospective observational cohort study included 305 patients with obesity and MASLD and 103 matched individuals with non-MASLD from January 2015 to April 2023, with a 12- month follow-up to monitor weight changes. Liver biochemistry, liver fat content with magnetic resonance imaging-based proton density fat fraction with Dixon sequence, and liver stiffness measurement via 2D-SWE were assessed at baseline and after 12 months. A validated weight trajectory regression model was applied to estimate the weight-loss plateau. Results: Individuals with MASLD and non-MASLD presented a similar timing of the weight plateau at 6 months, but patients with MASLD experienced less weight loss and maintained their weight plateaus longer compared to those with non-MASLD. Among patients with MASLD, a greater total weight loss (TWL) at 6 months was associated with better treatment response in hepatic steatosis and injury (all p < 0.001). Further multivariate logistic analysis showed that the 6-month TWL was an independent predictor of subsequent improvements in hepatic steatosis (OR: 0.78, 95% CI: 0.72-0.84) and alanine aminotransferase levels (OR: 0.82, 95% CI: 0.76-0.90) at 12 months. Conclusion: Patients with MASLD experienced gradual weight loss followed by a prolonged plateau, with the maximum reduction observed at 6 months. The degree of 6-month weight loss was a valuable prognostic factor for the 12-month hepatic treatment outcomes. Strategies to overcome this plateau are essential for improving long-term treatment efficacy in MASLD.