Fig. 1.

Schematic overview of normal and dysfunctional liver regeneration

Left side shows functional liver regeneration. Major hepatectomy induces drastic changes in the haemodynamic environment of the liver. An increase in shear stress leads to activation of liver sinusoidal endothelial cells, which in turn release nitric oxide (NO). NO together with cytokines released from Kupffer cells, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 promote liver regeneration. Right side shows dysfunctional liver regeneration. An overwhelming increase in portal pressure can cause ‘small-for-flow‘ syndrome. Excessive shear stress induces an overshooting inflammatory response, followed by neutrophil recruitment into the liver. This causes inhibition of liver regeneration, parenchymal necrosis, and hepatocyte apoptosis. LSEC, liver sinusoidal endothelial cells; ROS, reactive oxygen species.