Amyloidosis, change in macrophage number, and dysplasia in the liver of intravenous heroin users

__________________________________________________________________________________ Abstract. Apart from the usual morphological changes in the liver of intravenous heroin users such as vesicular and fatty changes, various forms of viral hepatitis and development of cirrhosis, the onset of amyloidosis, the change in the number of hepatic sinusoidal macrophages, and dysplastic changes are of particular significance from the forensic point of view since they can indicate heroin abuse, probably associated with alcohol effects, and they can also be a factor for the occurrence of severe morphological liver damage with a possible lethal outcome. A histopathologic and morphometric study of changes in the liver of heroin users aimed to show the presence of rarer morphologic changes in the liver as the indicators of heroin abuse, additional alcohol effects and viral infections. The present study included 40 autopsies of intravenous heroin users and 10 control autopsies. In order to facilitate the investigation, all autopsies of intravenous heroin users were grouped according to the duration of intravenous heroin intake into 4 groups: up to 2 years, 2-5 years; 5-10 years; over 10 years. Paraffin sections 5 μm thick, were stained by hematoxylin method (HE), van Gieson and Congo red. Morphometric investigation of sinusoidal macrophages in the liver was done using the M42 test system. Liver tissue samples taken to be tested for ultrastructural changes were fixed in glutaraldehyde and epon-embedded, and the analysis was done using transmission electron microscopy JEM 100 CX JEOL. Amyloidosis localized in portal tracts, mostly underneath the endothelium of the smaller branches of the hepatic artery was established in 9 cases (22,5%), out of which in 78% (in 7 of 9) the duration of intravenous intake lasted longer than 5 years. In 55,5% of cases (in 5 of 9), amyloidosis was associated with fatty alcohol changes. There was a statistically significant change in the number of sinusoidal macrophages in relation to the controls only in cases with chronic active hepatitis regardless of coexisting cirrhosis, whereas the other cases with established fatty alcohol changes showed no significantly higher number of these cells in relation to controls. Severe dysplastic changes were established in three cases with vesicular and fatty changes complicated with viral hepatitis, two of which were with coexisting cirrhosis; in all three cases (100%), the duration of intravenous heroin abuse lasted longer than 5 years. Long duration of heroin abuse is a condition for the occurrence of liver amyloidosis and dysplastic changes in the liver. The high percentage of association of amyloidosis with fatty alcohol changes in the liver points to the conclusion that the inactivation of hepatic sinusoid macrophages and the reduction of their enzymatic capacities occur due to additive, immunosuppressive effect of alcohol which may enable the onset of liver amyloidosis.