MASLD and MASLD-associated HCC: emerging biomarkers and therapeutic avenues

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading chronic liver disease on a global scale. With its increasing incidence and advances in research technologies, our understanding of the mechanisms, non-invasive diagnostic strategies and therapeutic approaches for MASLD and its more advanced forms, including metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), has substantially expanded. This article reviews the pathophysiological mechanisms underlying MASLD and its transition to more severe forms, evolving from well-established mechanisms including insulin resistance, abnormalities in lipid metabolism and inflammation, to recently explored novel mechanisms, such as immune regulation, RNA modification and gut microbiome. Additionally, emerging biomarkers for diagnosis and prognosis, such as non-invasive serum markers and genetic variants are highlighted. This review evaluates contemporary therapeutic strategies, with particular emphasis on the recent FDA approval of resmetirom and semaglutide, alongside other pharmacological agents currently in phase 3 clinical trials. It also discusses innovative interventions aimed at improving the management of MASLD and MASLD-HCC, specifically in the context of gut modulation and enhancing the efficacy of immunotherapy. The necessity for strategies aimed at early detection and multifactorial treatment approaches is critical to address the rising burden of MASLD and its complications, with a call for further research into personalised medicine and innovative multidisciplinary therapeutic targets.