Systematic Review: Pathophysiology of Hepatic Alterations Associated with Metabolic Syndrome

This systematic review details the pathophysiology of metabolic dysfunction–associated steatotic liver disease (MASLD), identifying it as the intrinsic hepatic manifestation of metabolic syndrome. The process is primarily triggered by insulin resistance, which disrupts lipid metabolism and promotes a massive influx of fatty acids into the liver, leading to lipotoxicity and oxidative stress. Under the “multiple-hit” model, factors such as chronic inflammation derived from dysfunctional adipose tissue, dysbiosis of the gut–liver axis, and genetic polymorphisms (such as those in the PNPLA3 gene) act synergistically to promote progression from simple steatosis to severe conditions such as metabolic dysfunction–associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, it is concluded that therapeutic management must be comprehensive, focusing on visceral obesity and systemic inflammation beyond the hepatic organ itself.