Mechanisms of liver regeneration in a clinical model for preoperative induction of liver hypertrophy prior to major liver resection

Abstract

The liver is a central organ for homeostasis and has the unusual and remarkable property of regeneration with rapid restoration of its volume and function. Liver regeneration (LR) is a very enigmatic and complex process involving numerous intra and extrahepatic signals and pathways. Interestingly, genetic knockdown studies have often demonstrated delays in the course of regeneration, but no single signal has been identified to be both sufficient and necessary for LR. Furthermore, LR can be modified by multiple patient, liver or trauma-related factors. As a consequence, diverse clinical applications have been developed and used extensively including hepatic resections to remove liver tumours, split liver transplantation from donors, portal vein occlusion, artificial support in acute liver insufficiency or cellular therapy. Recently, a surgical technique named associated liver partition with portal vein ligation for staged hepatectomy (ALPPS) has shown an unprecedented property of accelerating LR. This procedure results in a greater speed of cell hypertrophy in the future liver remnant when compared with the gold standard portal vein embolization (PVE). These techniques are used for preoperative optimization of a small future liver remnant, avoid postoperative liver failure and, in turn, improve morbidity and mortality. Unfortunately, tumoral progression has been observed after PVE precluding the potential of curative hepatectomy. The ALPPS procedure may speed this hepatic resection and increase resectability rates. However, due to its associated high morbidity and mortality rates, diverse groups have developed modifications of the ALPPS technique (ALPPS variants). This includes radiofrequency assisted liver partition ablation with portal vein ligation for staged hepatectomy (RALPPS). By associating a line of necrosis with radiofrequency ablation following portal vein ligation, this two-stage technique allows a safe and rapid LR without an increased morbidity or mortality associated with the procedure. Herein, a general review of the process of LR is presented as well as further research of the intrinsic mechanisms of LR induced by PVE and the ALPPS variant, RALPPS.