Specific metabolic impairments indicate loss of sustained liver improvements in metabolic dysfunction-associated steatotic liver disease treatment.

Abstract

High liver fat content (LFC) induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease (MASLD), while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) (≥30% decline relative to baseline) without worsening fibrosis results in improved histological severity and prognosis. However, the factors associated with the loss of sustained responses to treatment remain unclear, and we aim to identify them. Consecutive treatment-naïve MASLD patients between January 2015 and February 2022, with follow-up until April 2023, were included in this prospective cohort study. LFC quantified by MRI-PDFF and liver stiffness measurements (LSM) determined by two-dimensional shear wave elastography (2D-SWE) were evaluated at weeks 0, 24 and 48. MRI-PDFF response was defined as a ≥30% relative decline in PDFF values, and LSM response was defined as a ≥1 stage decline from baseline. A total of 602 MASLD patients were enrolled. Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks, the rate of loss of MRI-PDFF response was 29.4%, and multivariable logistic regression analyses showed that 24-week insulin resistance (IR), still regular exercise and caloric restriction after 24 weeks, and the relative decline in LFC were risk factors for loss of MRI-PDFF response. Loss of LSM response at 48 weeks occurred in 15.9% of patients, and multivariable analysis confirmed 24-week serum total bile acid (TBA) levels and the relative decline in TBA from baseline as independent predictors. No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response. MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis, respectively.