Metabolically–dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is increasingly recognized as a systemic disorder at the intersection of metabolic dysregulation, inflammation, and carcinogenesis. Progression from simple steatosis to metabolic dysfunction–associated steatohepatitis (MASH), fibrosis, and hepatocellular carcinoma (HCC) reflects the interplay between metabolic overload, oxidative stress, immune activation, and gut microbiota dysbiosis. In this review, we propose the Redox–Microbiota–Inflammatory Axis as an integrative framework linking metabolic stress to fibrogenesis and hepatocarcinogenesis. Nutrient excess and insulin resistance promote mitochondrial dysfunction and reactive oxygen species (ROS) generation, which activate redox-sensitive inflammatory pathways. Concurrently, gut-derived microbial products and metabolites enhance hepatic immune signaling through the gut–liver axis, creating a self-amplifying pathogenic loop. Understanding this interconnected network highlights biologically actionable pathways and supports emerging therapeutic strategies targeting oxidative stress, inflammation, and microbiota-driven mechanisms across the MASLD spectrum.
Nilo et al. (Thu,) studied this question.