Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu

Abstract

Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction post-transplantation. Cellular and biochemical processes occurring during hepatic ischemia-reperfusion are diverse and complex, and include the deregulation of the healthy phenotype of all liver cellular components. Nevertheless, a significant part of these processes are still unknown or unclear. The present review aims at summarizing the current knowledge in liver ischemia-reperfusion, but specifically focusing on liver cell phenotype and paracrine interaction deregulations. Moreover, the most updated therapeutic strategies including pharmacological, genetic and surgical interventions, as well as some of the scientific controversies in the field will be described. Finally, the importance of considering the subclinical situation of liver grafts when translating basic knowledge to the bedside is discussed.

Keywords: CINC; ENA-78; ET; Endothelium; GM-CSF; GdCl(3); HO-1; HSC; Hepatocyte; I/R; ICAM-1; IL; INF-γ; KC; KLF2; Kruppel-like factor 2; Kupffer cells; LSEC; MIP-2; NAD; NFκB; NO; PPAR; ROS; TNF; TXA(2); Transplantation; cytokine-induced neutrophil chemoattractant-1; eNOS; endothelial nitric oxide synthase; endothelin; epithelial neutrophil activating protein-78; gadolinium chloride; granulocyte-macrophage colony-stimulating factor; heme oxygenase-1; hepatic stellate cells; interferon-gamma; interleukin; intracellular adhesion molecule-1; ischemia-reperfusion; liver sinusoidal endothelial cells; macrophage inflammatory protein-2; nicotinamide adenine dinucleotide; nitric oxide; nuclear factor kappa B; peroxisome proliferator-activated receptor; reactive oxygen species; thromboxane A2; tumour necrosis factor.