Functional Liver Recovery After Major Hepatectomy: Integrating Hemodynamic Optimization and Oxidative Stress

Background: Major liver resections that include the removal of four or more Couinaud segments require precise assessment of the future liver remnant (FLR) to prevent post-hepatectomy liver failure (PHLF). Volumetry, although standard in surgical planning, does not always reflect true functional reserve, especially in steatotic, fibrotic or chemotherapy-damaged liver. Methods: This review proposes an integrative physiological framework of functional liver recovery after a major hepatectomy that connects preoperative functional assessments-indocyanine clearance (ICG-PDR), Liver Maximum Function Capacity test (LiMAx) and 99mTc-mebrofenin SPECT/CT-with perioperative hemodynamic, oxidative and metabolic parameters. A narrative literature review was performed using PubMed and Web of Science, covering publications from January 2000 to January 2025. The search combined keywords and MeSH terms such as major hepatectomy, liver regeneration, hemodynamic optimization, oxidative stress and post-hepatectomy liver failure. We focused on clinically relevant studies, including randomized controlled studies and consensus guidelines, and complemented the search by screening the reference lists of selected articles. When direct clinical evidence was limited, a physiologically grounded interpretation was used to support a pragmatic framework for perioperative management. Results: The framework integrates three complementary physiological domains that together determine functional liver recovery. The first relates to hemodynamic stability, including optimal maintenance of arterial and venous pressures as well as portal-splanchnic gradients, which support adequate perfusion and oxygenation of hepatocytes. The second addresses the balance between oxidative stress and antioxidant defense, where the key indicators are the level of lipid peroxidation and endogenous antioxidant capacity. The third domain evaluates the functional ability of the liver through dynamic tests of synthesis and metabolism, such as factor V, indocyanine clearance (ICG-PDR), and the LiMAx test. With the integration of these three domains, a functional profile of liver recovery can be defined, facilitating monitoring of the physiological response in real time and guiding individualized perioperative support to the individual needs of the patient. Conclusions: Functional recovery follows a dynamic continuum, progressing from early reperfusion stress through hemodynamic stabilization to progressive hepatocellular regeneration. Integration of functional FLR assessment with perioperative physiological monitoring may support more individualized prediction of the regenerative capacity and therapeutic decision-making. This physiology-guided perspective extends assessment beyond remnant volume alone to include functional recovery.