How Physiology and Pharmacology Shape Liver Regeneration: From Molecules and Cells to Trials

Liver regeneration is a tightly orchestrated compensatory response in which the remaining liver regains mass and function after liver injury or surgical resection. However, it does not fully restore its original anatomy. This process involves sequential priming, proliferative, and termination phases that are controlled by inflammatory cytokines, growth factor signaling, metabolic regulation, and extracellular matrix remodeling. Clinically, regenerative capacity plays a crucial role in situations such as partial hepatectomy, acute liver failure, and chronic liver disease. Unfortunately, it can be compromised by conditions like cirrhosis, steatosis, diabetes, and other systemic or local disorders. Current strategies to improve regeneration, such as portal vein modulation, cell-based therapies, organoid technology, and bioartificial liver support, show promise. However, they are limited by challenges including impaired engraftment, functional immaturity, technical complexity, and scalability restrictions. Against this background, the present review explores the pathophysiological basis of liver regeneration and evaluates the clinical evidence on nutritional and pharmacological interventions aimed at enhancing the natural liver repair mechanisms.