title: Ultrastructural liver pathology in patients with minimal liver disease and alpha 1-antitrypsin deficiency: a comparison between heterozygous and homozygous patients.
abstract: A light and electron microscopic investigation of liver tissue from three homozygous (Pi-type ZZ) and three heterozygous (Pi-type MZ) alpha 1-antitrypsin deficiency patients is presented. All had slightly elevated levels of serum amino transferases as the only signs of liver damage. Light microscopical investigation showed minor periportal fibrosis and periodic acid-Schiff-positive globules in the homozygous patients, but no specific findings besides fatty changes were seen in the heterozygous patients. Electron microscopical investigation was performed on periportal and centrilobular areas separately. In the three homozygous patients, dilatation of endoplasmic reticulum was found in many periportal liver parenchymal cells. In these cells, a marked increase in peroxisomes was also noted and in some instances they showed signs of cell necrosis. Evidence of Kupffer cell heterophagy of such cells was also found, thus indicating that they had died. Only in one liver parenchymal cell from one of the three heterozygous patients was evidence of a dilated endoplasmic reticulum found. No increase in peroxisomes was found and no apparent signs of liver cell necrosis were noted. An increased amount of lipofuscin-like material in the lysosomes was encountered in liver cells both from patients with homozygous and heterozygous alpha 1-antitrypsin deficiency. Based on these findings, it is suggested that cell death occurs in cells with a dilatation of the endoplasmic reticulum. If these findings are important for the pathogenesis in liver disease in alpha 1-antitrypsin deficiency, the present study suggests that the risk to develop liver disease is less in heterozygous patients since, with one exception, alterations of the same nature were not found in their hepatocytes.
mesh_terms: D000328:Adult; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007728:Kupffer Cells / Q000648:ultrastructure; D008062:Lipofuscin / Q000032:analysis; D008099:Liver / Q000648:ultrastructure*; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology*; D008247:Lysosomes / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010641:Phenotype; D012306:Risk; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D008062:Lipofuscin