Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption


Marie-Cécile Nollevaux, MD, Department of Pathology, Cliniques universitaires UCL de Mont-Godinne, Avenue Thérasse, 1, B5530–YVOIR, Belgium.
Tel: +32 81 42 30 13
Fax: +32 81 42 30 16
e-mail: marie-cecile.nollevaux@mont.ucl.ac.be


Abstract: 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.

Aims: 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 α 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).

Conclusion: 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.