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.