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

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.