Pathophysiology

Cirrhosis is characterized by irreversible diffuse fibrosis of the liver (the final common pathway for chronic liver diseases).

Pathogenesis is multifactorial.

• Different liver cells and cytokines are involved in the activation and progression of liver fibrosis.

• Cytokine‑mediated activation of hepatic stellate cells has been identified as a central element for developing fibrosis.

The following three mechanisms have been described for all types of liver cirrhosis: [5]

1. Degeneration and necrosis of hepatocytes

   • Activated Kupffer cells destroy hepatocytes, activate hepatic stellate cells, and promote inflammation.

   • Inflammatory cytokines (e.g., TGF-β, PDGF) → hepatocyte apoptosis and hepatic stellate cell activation → excess collagen production

2. Fibrotic tissue and regenerative nodules replace the liver parenchyma

   • Hepatocyte destruction triggers repair mechanisms → excess formation of connective tissue (fibrosis)

   • Excessive connective tissue in periportal zone and centrilobular zone → regenerative nodules and fibrous septa → compression of hepatic sinusoids and venules → ↑ portal vein hydrostatic pressure → intrasinusoidal hypertension → ↓ functional sinusoids

3. Loss of liver function: sinusoidal capillarization → loss of fenestration and scar tissue formation→ impaired substrate exchange → loss of normal liver function (exocrine and metabolic)