Metabolic Comorbidities Modulate the Impact of Weight Loss on Liver Fibrosis in MASLD: A Real World Prospective Cohor Study

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health challenge. While weight loss is a recognized treatment, its effectiveness across different metabolic profiles remains poorly quantified. We employed advanced imaging techniques to precisely evaluate hepatic responses to weight reduction in MASLD patients with varying metabolic complexity. Methods In this prospective cohort study of 724 MASLD patients undergoing lifestyle interventions, we quantified changes in liver fat content (LFC) and liver stiffness measurements (LSM) using MRI-proton density fat fraction and FibroScan®, respectively. A subset of 146 patients underwent liver biopsies. MASLD remission was defined as > 30% relative reduction in LFC. We developed decision tree models for predicting MASLD improvement and analyzed the relationship between weight reduction and hepatic parameters across metabolic subgroups. Results Our cohort exhibited significant metabolic burden: 40% had metabolic syndrome (MetS), 23% had diabetes, and 45% were obese. Weight loss > 5% resulted in MASLD remission in 74% of patients (n = 100). Each 1 kg/m² BMI reduction corresponded to a 2.4 ± 0.1% absolute decrease in LFC. However, improvements in liver stiffness varied markedly by metabolic status. Per 1 kg/m² BMI reduction, LSM decreased by 0.4 kPa versus 0.9 kPa in patients with versus without MetS, 0.6 kPa versus 1.1 kPa in obese versus overweight patients, and 0.3 kPa versus 0.7 kPa in patients with versus without diabetes. Conclusion In patients with MASLD and metabolic comorbidities, weight loss demonstrates attenuated therapeutic efficacy in improving liver fibrosis, underscoring the necessity for intensified interventions to address fibrosis progression in high-risk metabolic subgroups. Trial registration: The study was registered with the Chinese Clinical Trial Registry (ChiCTR2100054743, registration date: December 26, 2021, https://www.chictr.org.cn) and received ethical approval from the First Hospital of Jilin University (Ethical Approval Number: 19K096001).