The pathophysiological role of portal hypertension in metabolic dysfunction-associated steatotic liver disease

Portal hypertension (PH) develops when static lesions such as steatosis, fibrosis, and cirrhotic nodules accumulate within the liver due to alcohol, metabolic syndrome, or other etiologies. In addition, dynamic components further enhance the hepatic vascular resistance (HVR) caused by activated hepatic stellate cells (HSCs) and sinusoidal endothelial cells (SECs). Both alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are significant global health burdens, and knowledge on the pathophysiology behind the development of complications to PH is crucial. Hepatic cells with compromised function, such as hepatocytes, HSCs, and SECs, are deeply involved in the hemodynamic changes, impaired degradation of vasoactive substances, production of vasodilators, immune function, and mechanosensing. PH remains the main driver of liver-related complications, but it is often measured lower than expected in MASLD, partly because of the presence of inter-sinusoidal communications. The aim of this overview is to highlight pathophysiological aspects of PH in ALD and MASLD.