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P Barlet

Publications and source records attributed to P Barlet.

7 recordsLinked to original sources

Cellular and matrix changes in drug abuser liver sinusoids: a semiquantitative and morphometric ultrastructural study.

The aim of the present work was to analyse, at the ultrastructural level, the action of heroin of 150 centrilobular sinusoids from liver biopsies of five intravenous drug abusers, who presented clinical and biological manifestations of hepatic impairment. A comparative study of 90 sinusoids from liver biopsies of three control patients was performed. Electron microscopic observations showed a thickening of the sinusoidal wall related to endothelial cell hypertrophy and to fibrosis of the space of Disse. This was generally associated with basement-membrane-like material and hepatocyte microvilli flattening. In addicts, hepatic vascular pole changes were a constant finding, accompanied by interhepatocyte space disjunction and perisinusoidal collagenization. Morphometric assessment confirmed a significant increase of sinusoidal wall surface, endothelial cell body and processes and Ito cell process surface was significantly different between the patient groups. This cellular hypertrophy may represent hyperactivation of the sinusoidal cell functional capacity, triggering the fibrogenesis in the space of Disse. While this mechanical barrier might hinder the free exchange through the space of Disse, it may equally well protect the liver against heroin toxicity.

Adult↗

Vascular hepatotoxicity related to heroin addiction.

The hepatotoxic effect of heroin has been demonstrated in liver biopsies by morphometric analysis of four groups of patients: twenty-one drug abusers (DA) at the time of the biopsy, eighteen patients who had stopped drug consumption for at least six months (ex-DA), twelve patients with post-transfusional chronic active hepatitis (PTCAH), and eleven controls (CONTROL). Semiquantitative assessment showed the extent of sinusoidal dilatation and the inflammatory and fibrotic reaction in the terminal hepatic vein (THV). Thickening and cellularity of the venular wall and the volume density of sinusoidal lumen (Vsl) in the Zone I and III of the hepatic acinus, were also evaluated. The morphometric analysis used computerized measurements. In DA, the sinusoidal dilatation (100% of cases), the sinusoidal and THV inflammation (81% and 67.7%, respectively), localized mainly in the centrilobular zone, were more pronounced than in ex-DA, in patients with PTCAH and in CONTROL (significantly different P less than 0.0001). Conversely, the fibrotic reaction (perisinusoidal fibrosis--44.4% and perivenular fibrosis--61.1%) was more frequent in ex-DA. The THV inflammation in DA was replaced by a fibrotic matrix deposit in the THV wall (wall surface/internal surface = 2.72 +/- 0.37 in ex-DA; 1.38 +/- 0.32 in DA; 0.87 +/- 0.14 in PTCAH and 0.45 +/- 0.03 in CONTROL--significantly different P less than 0.001), associated with a perisinusoidal fibrosis, after drug withdrawal. Moreover, there was significantly decreased venular wall cellularity in ex-DA (wall surface/mesenchymal cells = 949 +/- 158 in ex-DA; 622 +/- 40 in DA; 619 +/- 61 in PTCAH; 547 +/- 23 in CONTROL--P less than 0.001). Semiquantitative and morphometric data suggest that these vascular lesions and their reversibility may be due to the direct hepatotoxic effects of heroin.

Adult↗