Liver fibrosis and its regression
- Mechanism
Long injury turns quiet fat-storing stellate cells into scar makers; if the cause stops, part of the scar can be removed.
What it is
Hepatic fibrosis is the deposit of collagen in response to chronic injury. The main scar-forming cell is the hepatic stellate cell of the space of Disse, which loses its vitamin A droplets and becomes a contractile myofibroblast. Regeneration from hepatocytes and progenitor cells (the ductular reaction) runs alongside. Fibrosis was once thought permanent, but when the injury is removed (for example, viral cure or alcohol abstinence) septa can thin and regress.
Structure
- Early: portal fibrous expansion and pericellular (chicken-wire) fibrosis in zone 3 in steatohepatitis.
- Then: portal-to-portal and portal-to-central septa (bridging fibrosis), best seen with trichrome.
- Ductular reaction: small irregular ductules with inflammatory cells at the edge of portal tracts and septa.
Step by step
- Chronic injury kills hepatocytes and activates Kupffer cells and lymphocytes.
- TGF-β, PDGF and oxidative stress activate stellate cells in the space of Disse.
- Stellate cells lose their vitamin A and turn into contractile myofibroblasts.
- They lay collagen in the space of Disse; sinusoids lose fenestrae and the exchange with hepatocytes fails.
- Myofibroblast contraction raises sinusoidal resistance and portal pressure.
- Septa link portal tracts and central veins; nodules form: cirrhosis.
- If injury stops, stellate cells become inactive or die and metalloproteinases slowly degrade scar.
In the lab
- Biopsy stage is scored on a 0 to 4 scale (no fibrosis to cirrhosis) by trichrome and reticulin stains.
- Noninvasive estimates: elastography (liver stiffness) and serum fibrosis scores.
Test yourself
Think of the answer, then tap the question to see it.
Which cell produces most of the collagen in liver fibrosis?
The activated hepatic stellate cell (Ito cell) of the space of Disse, transformed into a myofibroblast.
What is sinusoidal capillarization?
Loss of endothelial fenestrae and deposit of basement membrane in the space of Disse, which blocks exchange between plasma and hepatocytes.
Can liver fibrosis regress?
Yes: when the cause is removed, stellate cells deactivate and scar is degraded, although advanced cirrhosis rarely returns to normal.
Elsewhere in DurgiPedia
- Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells
- Extracellular matrix: collagen types, elastin, ground substance
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hepatic Cirrhosis (StatPearls (NCBI Bookshelf), 2022).
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Representative model, for educational purposes only.