Protease-Activated Receptor 2 and Its Role in the Progression from Metabolic-Disfunction Associated Steatotic Liver Disease to Hepatocellular Carcinoma

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently emerged as the predominant aetiology of chronic liver disease worldwide. This condition can progress to hepatocellular carcinoma (HCC) through various pathogenetic mechanisms. Briefly, metabolic dysfunction, which may occur in genetically susceptible individuals, disrupts lipid metabolism homeostasis. This imbalance leads to increased oxidative stress and DNA damage. Concurrently, chronic inflammation intensifies, impairing immune surveillance and facilitating HCC progression. Recent research has shed light on the significant role of Protease-activated receptor 2 (PAR2) in metabolic regulation. PAR2 is not only pivotal in inflammatory and fibrotic process but has also been identified as a key metabolic regulator. Given its multifaceted functions, PAR2 has become a focal point in studies exploring obesity, MASLD progression and HCC development. This review aims to synthesize the major findings from this growing field of research, offering insights into the intricate relationship between PAR2, metabolic dysfunction, and liver disease progression.