Associations of episodic and tonic appetite-related signals with malnutrition and appetite dysregulation in end-stage liver disease.

Malnutrition is highly prevalent in end-stage liver disease (ESLD), while being strongly associated with sarcopenia and poor prognosis in this population. The physiological regulation of energy intake is influenced by tonic signals, reflecting body composition and metabolic demands, and episodic signals, arising from gastrointestinal peptides, that remain to be better explored in the context of ESLD. The present narrative review analyzed 94 studies that characterises circulating concentrations of ghrelin, CCK, PYY, GLP-1 and leptin in cirrhosis and hepatocellular carcinoma. Overall, in patients with ESLD, orexigenic signaling, particularly from ghrelin and Fat-Free Mass (FFM) appears blunted, while anorexigenic peptides (CCK, PYY, GLP-1) are frequently elevated, prolonging satiety. Leptin regulation is inconsistent, reflecting both inflammation-driven increases and fat mass-related decreases. These disturbances converge toward a mismatch between elevated metabolic requirements and insufficient energy intake. Understanding how ESLD disrupts appetite-regulating pathways may help design new strategies to restore nutritional balance and improve clinical outcomes.