Metabolic Modulation for Liver Regeneration in Hepatocellular Carcinoma: From Biological Mechanisms to Precision Regenerative Medicine

Abstract

Abstract Background: Liver regeneration is essential after hepatectomy, but it is frequently impaired in patients with hepatocellular carcinoma (HCC) due to cirrhosis, metabolic dysfunction, sarcopenia, malnutrition, aging, and systemic inflammation. Post-hepatectomy liver failure remains a major clinical challenge. Objective: This review summarizes metabolic mechanisms underlying liver regeneration and explores metabolic vulnerabilities in patients with HCC, along with emerging therapeutic strategies to enhance regenerative capacity. Methods: A narrative review of current literature was conducted focusing on hepatic regenerative biology, metabolic reprogramming, and clinical metabolic interventions relevant to perioperative liver care. Results: Liver regeneration is regulated not only by growth factor signaling but also by coordinated metabolic reprogramming, including energy metabolism, lipid oxidation, amino acid homeostasis, mitochondrial function, and inter-organ crosstalk. Patients with HCC often exhibit impaired regenerative metabolism. Emerging interventions include nutritional optimization, branched-chain amino acid supplementation, L-carnitine administration, exercise-based prehabilitation, and modulation of the gut–liver axis. L-carnitine is highlighted as a mitochondrial modulator with potential benefits for hepatic function and muscle preservation. Conclusion: Targeting metabolic pathways represents a promising strategy to enhance liver regeneration. Integrating metabolic biomarkers and personalized interventions may improve perioperative outcomes in HCC patients undergoing hepatectomy.