Precision imaging in chronic liver disease management.

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over a quarter of the global population, with up to 30% developing Metabolic Dysfunction-Associated Steatohepatitis (MASH), a progressive form that can silently lead to fibrosis, cirrhosis, and liver cancer. Current diagnostic methods, including blood-based scores and imaging, are insufficient for early detection, leading to late-stage diagnoses in most patients. Liver biopsy remains the diagnostic gold standard but is invasive, costly, and prone to high inter- and intra-reader variability, limiting its utility in routine care and clinical trials. Our research highlights myosteatosis-fat infiltration in skeletal muscle-as a potential early, non-invasive marker of MASH. In preclinical models and clinical studies, myosteatosis correlated with the presence of MASH and distinguished it from isolated steatosis. Notably, reductions in myosteatosis following interventions such as bariatric surgery or dietary regimens were associated with histological improvements in MASH, suggesting a potential role in predicting treatment response. In larger cohorts, myosteatosis was identified as a strong predictor of all-cause mortality. In parallel, we utilized a VCAM- 1-targeted molecular imaging technique and demonstrated a high accuracy in detecting inflammation in preclinical MASH models. This technology is now advancing to clinical trials for validation in humans. Taken together, our data support that targeted medical imaging may enable early, non-invasive diagnosis and monitoring of MASH, reducing reliance on liver biopsy and improving patient outcomes.