What cell is responsible for cirrhosis?

The primary cell responsible for the development and progression of liver cirrhosis is the hepatic stellate cell (HSC).

The Central Role of Hepatic Stellate Cells (HSCs)

Hepatic stellate cells are a type of nonparenchymal cell residing in the space of Disse within the liver, nestled between liver sinusoids and hepatocytes. In a healthy liver, HSCs are typically in a quiescent (inactive) state, primarily functioning in vitamin A storage and contributing minimally to the liver's structure.

However, when the liver sustains chronic injury from various causes—such as prolonged alcohol abuse, viral infections (e.g., hepatitis B or C), non-alcoholic fatty liver disease (NAFLD), or autoimmune conditions—hepatic stellate cells undergo activation. This transformation is a critical step in the pathogenesis of liver fibrosis, which is the precursor to cirrhosis.

Upon activation, HSCs transform into myofibroblast-like cells and acquire several key functions that drive the progression of liver disease:

• Excessive Extracellular Matrix (ECM) Production: Activated HSCs become the main producers of scar tissue components, primarily collagen. This overproduction and deposition of ECM lead to the accumulation of fibrous tissue, distorting the liver's normal architecture and impairing its function.
• Contractile Properties: They gain contractile capabilities, which can contribute to increased resistance to blood flow within the liver, a hallmark of portal hypertension in cirrhosis.
• Secretion of Inflammatory Mediators: Activated HSCs release various signaling molecules, including cytokines and chemokines, that perpetuate inflammation and recruit other immune cells, further fueling the fibrotic process.

The persistent accumulation of this scar tissue, largely orchestrated by activated HSCs, fundamentally alters the liver's structure, leading to the formation of regenerative nodules and widespread fibrosis characteristic of cirrhosis.

Other Cells Involved in Cirrhosis Pathogenesis

While hepatic stellate cells are the primary fibrogenic cells, the development and progression of liver fibrosis and cirrhosis are complex processes that involve the interplay of multiple cell types within the liver. Both hepatic parenchymal cells (hepatocytes) and other nonparenchymal cells contribute significantly to the initiation and progression of the disease.

These include:

• Liver Sinusoidal Endothelial Cells (LSECs): These cells line the hepatic sinusoids and are crucial for maintaining liver function and regulating blood flow. In liver injury, LSECs can become dysfunctional, leading to a process called "capillarization," which impairs the exchange of substances between blood and hepatocytes and contributes to the progression of fibrosis.
• Kupffer Cells (KCs): As the liver's resident macrophages, Kupffer cells play a key role in the immune response to liver injury. They can release pro-inflammatory and pro-fibrotic signals that directly activate hepatic stellate cells, thereby promoting scar tissue formation.
• Hepatocytes (Parenchymal Cells): These are the liver's main functional cells and the primary targets of injury. Their damage, death, and subsequent attempts at regeneration contribute to inflammation and can indirectly stimulate the activation of hepatic stellate cells, further accelerating the fibrotic process.

Summary of Cellular Involvement in Cirrhosis Development:

Understanding the intricate interactions among these diverse cell types is essential for comprehending the multifaceted pathogenesis of liver cirrhosis and for developing effective therapeutic strategies to combat this debilitating disease. For more detailed information on the mechanisms of liver fibrosis and cirrhosis, you can explore resources on liver fibrosis pathogenesis and the specific role of hepatic stellate cells in liver disease.