Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption.
Hypervitaminosis A-related liver toxicity may be severe and may even lead to cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells (HSC), which are prone to becoming activated and acquiring a myofibroblast-like phenotype, producing large amounts of extracellular matrix.


OBJECTIVE
In order to assess the relationship between vitamin A intake, HSC activation and fibrosis, we studied nine liver biopsies from patients belonging to a well-characterized series of 41 patients with vitamin A hepatotoxicity.


METHODS
Fibrosis was underlined by Sirius-red staining, whereas activated HSC were immunohistochemically identified using an antibody against alpha smooth muscle actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal and total activated HSC was quantified by the point-counting method.


RESULTS
Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to severe architectural distortion. There was a significant positive correlation between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A (P=0.004).


CONCLUSIONS
The close correlation between the severity of perisinusoidal fibrosis and the daily dose of the retinol intake suggests the existence of a dose-effect relationship.
Nollevaux
M-C
MC
Department of Pathology, Cliniques universitaires Saint Luc, University of Louvain, Brussels, Belgium. marie-cecile.nollevaux@mont.ucl.ac.be
Guiot
Y
Y
Horsmans
Y
Y
Leclercq
I
I
Rahier
J
J
Geubel
A P
AP
Sempoux
C
C
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D049108:Cell Enlargement / Q000187:drug effects; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D006986:Hypervitaminosis A / Q000139:chemically induced* / Q000473:pathology; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014801:Vitamin A / Q000009:adverse effects*
D000199:Actins; D015415:Biomarkers; D014801:Vitamin A