Recent Advances in miRNA-Based Therapy for MASLD/MASH and MASH-Associated HCC

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, affects over one billion adults worldwide. It can progress to more severe conditions, like metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma (HCC). Recent studies have highlighted the role of microRNAs (miRNAs) in this progression due to their ability to regulate genes involved in lipid metabolism, inflammation, fibrosis, and cell proliferation. Modulating miRNAs through synthetic molecules represents a promising therapeutic strategy. Preclinical models demonstrate that miRNA-based therapies can reduce liver inflammation and fibrosis and inhibit tumorigenesis, potentially delaying or preventing HCC onset. However, challenges such as delivery mechanisms, side effects, and long-term safety remain to be addressed. This review, focusing on recent preclinical and clinical studies, explores the pharmacological potential of miRNA-based interventions to counteract MASLD/MASH and their progression to HCC. It provides insights into an emerging field with significant implications for liver disease treatment.