Modulating the Future Liver Remnant before Major Hepatectomy: A Critical Appraisal of the Comparative Effectiveness and Safety of Venous, Surgical, and Radiation-based Augmentation Strategies

Abstract

Major and extended hepatectomy remains the principal curative treatment for many primary and secondary hepatic malignancies, yet an inadequate future liver remnant (FLR) continues to preclude resection in a substantial proportion of patients and is the dominant determinant of post-hepatectomy liver failure (PHLF), the leading cause of perioperative death after extensive resection. Several strategies now compete to augment the remnant before surgery: percutaneous portal vein embolization (PVE), surgical portal vein ligation within a planned two-stage hepatectomy, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and its variants, combined portal and hepatic vein occlusion delivered as liver venous deprivation or double vein embolization, and radiation lobectomy achieved through unilobar transarterial radioembolization. This critical narrative review evaluates the comparative effectiveness and safety of these approaches rather than cataloguing them individually. Evidence was drawn primarily from indexed peer-reviewed literature identified through MEDLINE and complementary scholarly sources, with reference-level verification. The synthesis distinguishes what is well supported from what remains provisional. PVE is effective and safe but is limited by an interval dropout attributable to insufficient hypertrophy or interval tumour progression. ALPPS produces the most rapid volume gain and the highest resection rates, at the cost of higher, though now attenuated, perioperative risk. Combined venous deprivation achieves volume gains and growth kinetics approaching those of ALPPS through a percutaneous route, but high-quality comparative outcome data remain limited. Radiation lobectomy augments the remnant more slowly while adding local tumour control. A recurring problem is the dissociation between the volume a technique produces and the clinical benefit it confers, and the near-absence of randomised comparisons for the newer venous techniques. The review identifies priorities for adequately powered trials that report function alongside volume, oncological endpoints, and patient-centred outcomes, and argues that technique selection should be individualised to tumour biology, parenchymal quality, and institutional expertise rather than driven by volumetric performance alone.