Portal inflow restriction enhances liver regeneration and decreases liver injury after major liver resection

Abstract

Backgroundl: Extended liver resection leads to acute hyperperfusion of the remnant liver associated with structural and functional changes in the remaining liver tissue. In this study, we explored if reduction of the hepatic hyperperfusion impacts on liver injury and regeneration. Methods: Extended partial hepatectomy was performed in pigs and mice. Liver regeneration was assessed in mice and alterations of hemodynamic parameters, oxygen uptake and mitochondrial function was assessed in pigs. A vascular occluding device was designed to keep portal flow at 70% of the preoperative flow (intervention group) and compared to animals where portal flow was not manipulated (control group). Results: In pigs without portal inflow restriction, extended (70%) partial hepatectomy led to a persistent portal hyperperfusion with an increase in relative portal flow from 75ml/min/100g to 250ml/min/100g. In the intervention group, AST and ALT levels were reduced after portal inflow restriction compared to the control group. Hepatocellular proliferation was assessed in mice in which markers of proliferation were higher after partial portal vein ligation compared to untreated controls. Electron microscopy revealed reduced sinusoidal injury after portal inflow restriction. Conclusion: Liver injury after major liver resection is at least in part mediated by portal hyperperfusion. Portal inflow restriction reduces liver injury and increases liver regeneration after extended liver resection.