What is the physiology of hepatic (liver) regeneration?

From the Guidelines

The liver has a unique and remarkable ability to regenerate itself after injury or resection, with the exact trigger of liver regeneration remaining elusive, but thought to be related to a combination of peri-portal inflammation and the diversion of portal venous blood to the future liver remnant (FLR) 1.

Key Factors in Liver Regeneration

• The increase in FLR volume after portal vein embolization (PVE) is due to both clonal expansion and cellular hypertrophy, with the extent of post-embolization liver growth proportional to the degree of portal flow diversion 1.
• The portal venous system plays a crucial role in liver regeneration, with PVE being a widely used technique to optimize FLR volume before major hepatic resection 1.
• The future liver remnant (FLR) volume is critical to avoid post-operative liver failure, with a minimum of 25-30% of the total liver volume required in patients with normal liver function, and more than 40% required in patients with chronic liver disease 1.

Mechanisms of Liver Regeneration

• Rapid hypertrophy is seen in the FLR after resection, with restoration of liver mass and function within a few weeks 1.
• Hepatic ischemia-reperfusion injury, parenchymal congestion, and reduced phagocytic ability can all negatively impact the regenerative capacity of the liver 1.
• Portal vein embolization (PVE) is a technique used to optimize FLR volume before major hepatic resection, with a marked decrease in liver failure and 90-day mortality in patients with colorectal liver metastasis undergoing major liver resection 1.

From the Research

Physiology of Hepatic Regeneration

The physiology of hepatic regeneration is a complex process involving the coordinated effort of various cell types and molecular mechanisms. The liver's ability to regenerate itself is crucial for recovery from injury or disease.

Cell Sources and Influencing Factors

• Hepatocytes, biliary epithelial cells, hepatic progenitor cells, and human liver stem cells can serve as cell sources for liver regeneration 2.
• The background of the liver, including fibrosis and steatosis, influences regeneration by creating different microenvironments and signal molecule interaction patterns 2.
• Factors such as partial hepatectomy, aging, platelets, nerves, hormones, bile acids, and gut microbiota are also involved in the process of liver regeneration 2, 3, 4.

Molecular Mechanisms

• The IL-6/STAT3 and PI3-K/PDK1/Akt pathways play pivotal roles in regulating hepatocyte proliferation and cell growth, respectively 3, 5.
• Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) receptors are involved in triggering regenerative stimuli 4, 6.
• Cytokines such as IL-6, TNF-alpha, and growth factors like HGF and TGF-alpha are important for liver regeneration 3, 6.

Regeneration Process

• The regeneration process consists of initiation, proliferation, and termination phases, with hepatocyte proliferation being a key component 3, 5.
• Programmed cell death may interfere with liver regeneration in pathological situations, but it also plays a role in the termination phase of normal liver regeneration 5.
• The liver's ability to regenerate itself is essential for maintaining body homeostasis, and the hepatostat function helps restore the organ to its original mass 4.