It took millennia to understand how the liver regenerates after an infection such as hepatitis, or after surgery.


As Dr. Roberto Ceriani, Head of the Hepatological Day Hospital and Interventional Hepatology Section at Humanitas explains: “Although the mechanisms are not fully known, liver regeneration remains one of the most curious features of the liver. In fact, the organ grows again without losing its functions of synthesis, detoxification and metabolism of substances. The fact that the liver is an organ that continuously receives blood rich in nutrients but also in toxins from the intestine, could be the reason why the liver is equipped with this unique regenerative ability.


How does regeneration work?

The surgical removal of large amounts of liver (hepatectomy), up to two thirds, causes alterations in the balance of functions that are perceived by the organ, and guide the restoration process.

“The regeneration of liver cells is due to several factors that activate and deactivate signaling mechanisms throughout the process – continues Dr. Ceriani. In particular, a type of cell called quiescent, i.e. not yet differentiated and therefore not yet with specific functions, has a high capacity for regeneration and transformation. To activate the regeneration process, the quiescent cells need signals from various types of intrahepatic or extrahepatic cells, introduced into the organ by the portal vein circle. Between these cells we may find:

Mythogens, primary or auxiliary, or growth factors that can induce cell proliferation and duplication (the growth factor of hepatocytes, liver cells, the epidermal growth factor and the transforming one, interleukin 6, a protein that is activated in response to cell damage, and the tumor growth factor).


MicroRNAs that play a role in regulating the cell cycle.


Leukocytes, necessary for liver regeneration, macrophages, lymphocytes, eosinophils.


Platelets: they play a critical role in cell proliferation, their action is mediated by serotonin which induces liver mitosis, i.e. reproduction of cells identical to the original nucleus.


Sinusoidal endothelial cells that are a source of growth factors and are responsible for new vascularization.


Starred liver cells: These are found near the hepatic sinusoids that make up the liver’s capillary network, and are essential in ending liver regeneration.


Biliary epithelial cells: main source of substances that activate macrophages.


In the process of liver regeneration, changes also occur in the metabolism of lipids and glucose, such as transient liver steatosis that is established in the first phase of regeneration and serves the cell for energy production, but also in the pressure of the vein port that “brings” to the remaining liver the same amount of blood resulting in portal hypertension, a mechanism that also seems to induce regeneration. Finally, as after hepatectomy, the loss of liver tissue stimulates the biliary flow that activates the regulation of bile acids, which, in experimental models, have been shown to increase liver regeneration,” explained the specialist.


How long does the process take?

If in the myth of Prometheus, the great Titan was condemned by Zeus because he had given fire to human beings and his liver was devoured every night by an eagle, but it regenerated again the following morning, in reality the process of regeneration of the liver is not as rapid as in the myth; in fact, the greatest activity of liver regeneration occurs on the third day after the injury, while complete recovery takes place after 5-7 days.