Quantitative studies on liver fibrosis and alpha-smooth muscle actin expression in heroin abusers

Lobular hepatic fibrosis and the presence of myofibroblasts were studied in heroin abusers, by quantitative automatic image analysis. Nineteen addicts (DA) and thirteen patients having stopped consumption (exDA) were compared to a non-addict group (CONTROL). Addicts, all anti-HIV and HBsAg negative, showed increased transaminase levels. Hepatitis C markers were ot available, at the time of biopsy. The surface of the centrolobular fibrosis, measured on picrosirius stained slides, was respectively 1.9 and 3.5 times larger in DA and exDA than in CONTROL (p < 0.0001). Immunolabelling with an alpha-smooth muscle actin antibody (alpha-SMA) revealed stellate cells in a perisinusoidal location, mainly in areas of matrix thickening in the space of Disse. Morphometric analysis of alpha-SMA expression showed significant differences between the three groups of patients, p < 0.0001 (CONTROL: 198.06 +/- 5.59 microns2; DA: 2227.91 +/- 88.02 microns2; exDA: 3469.10 +/- 154.98 microns2). The surface density of collagen and of alpha-SMA reactivity was also significantly different between these groups (p < 0.0001). These data strongly suggest that heroin is responsible for an early and progressive centrolobular liver fibrosis, occurring simultaneously with a myofibroblastic response. It might represent a reparative phenomenon arising from a direct vascular injury, leading to an impairment of blood-hepatocyte exchange.