New Review Maps Molecular Drivers of Metabolic Dysfunction-Associated Steatohepatitis and Liver Cancer

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver condition worldwide, with its progressive stage, metabolic dysfunction-associated steatohepatitis (MASH), serving as a key risk factor for fibrosis, cirrhosis and hepatocellular carcinoma. This review synthesizes a decade of research on the disease’s pathogenesis, covering insulin resistance, genetic risk alleles, disturbed hepatic lipid handling, adipose dysfunction, immune-mediated inflammation, fibrogenesis and gut-liver axis perturbations.

It highlights how these insights are translating into clinical tools, including polygenic risk scores for disease progression and targeted therapies that curb hepatic lipogenesis or modulate mitochondrial function. The authors evaluate recent phase 2 and 3 trials of agents such as pan-PPAR agonists, resmetirom and mitochondrial uncouplers, and discuss future directions for preventing the MASH-to-cancer transition.