Human-Mouse Convergence in Metabolic Dysfunction-Associated Steatotic Liver Disease: Mouse Model Selection and Non-Invasive Diagnostic Strategies

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a global health priority affecting approximately 30% of the population. It represents the hepatic manifestation of metabolic syndrome, potentially progressing from simple steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. This review aims to compare current knowledge of MASLD in mouse models and humans, focusing on pathophysiology, histological phenotypes, and the role of preclinical imaging as a non-invasive translational screening tool. Methods: A literature search was conducted in PubMed and Web of Science to identify English-language publications from January 2020 to March 2026 on murine models and imaging techniques for MASLD, using pertinent keywords. Attention was given to highlighting similarities and differences between human and murine approaches. Results: MASLD arises from complex interactions between genetics, sedentary lifestyles, and imbalanced diets. While mouse models have been refined to capture the multifactorial interplay driving disease progression and are still essential for drug development, no single model fully mirrors the human condition. Histological assessment remains an essential tool for MASLD staging, in both humans and mouse models. However, imaging is increasingly emerging as an important complementary technique to non-invasively investigate MASLD. Conclusions: Mouse models are essential to address specific mechanistic and therapeutic questions, but understanding of their limitations and strengths is crucial for translational research. Integrating phenotype-driven approaches in both humans and mice, combining traditional histology, quantitative imaging, and metabolic profiling, as well as longitudinal, combined, and humanized preclinical models, will enhance translational alignment and accelerate the development of therapies for MASLD.