Early Changes in Peripancreatic Mesenteric Fat Beyond Weight Loss Predict Durability of Hepatic Improvements in MASLD

ABSTRACT Aims Various visceral adipose tissue depots exhibit heterogeneous metabolic properties. This study aims to explore whether specific abdominal fat compartments differentially predict loss of sustained treatment response to lifestyle interventions in metabolic dysfunction‐associated steatotic liver disease ( MASLD ). Materials and Methods Consecutive treatment‐naïve MASLD patients were prospectively enrolled from January 2015 to March 2024, with a 96‐week follow‐up period. Liver fat content, preperitoneal fat thickness ( PFT ), peripancreatic mesenteric fat thickness ( MFT1 ), periumbilical mesenteric fat thickness ( MFT2 ) and perirenal fat thickness ( PrFT ) were quantified using magnetic resonance imaging. Liver stiffness measurement ( LSM ) was assessed by 2D ‐ SWE . Treatment responses were evaluated at 48 and 96 weeks, and the primary outcome was loss of response at 96 weeks. Results A total of 631 MASLD patients (mean age: 41.5 ± 13.8 years; 72.0% male) were included. Logistic regression analyses revealed that a greater 48‐week relative decrease in MFT1 (per 10% relative reduction), rather than in MFT2 , PFT or PrFT , was independently associated with lower odds of losing MRI ‐ PDFF response ( OR : 0.48, 95% CI: 0.34–0.69, p < 0.001) and LSM response ( OR : 0.53, 95% CI: 0.28–0.99, p = 0.046) at 96 weeks. Receiver operating characteristic curve analyses indicated that relative changes in MFT1 showed discriminatory ability for the loss of MRI ‐ PDFF and LSM responses, with areas under the curves of 0.70 (95% CI: 0.64–0.76) and 0.77 (95% CI: 0.67–0.88), respectively. Conclusions Early changes in MFT1 were associated with subsequent loss of response in hepatic steatosis and fibrosis, suggesting potential prognostic value for hepatic response durability in MASLD .