Marked ultrastructural abnormalities observed in hepatocyte mitochondria, especially their polymorphism in the form of MMC and loss of mitochondrial cristae, accompanied by foamy cytoplasm, clearly indicate a major role of these organelles in the morphogenesis of pediatric NASH. Our findings seem to prove the high effectiveness of electron microscopy in the diagnosis of the disease.

KCs are involved in the morphogenesis and development of pediatric NASH. Engulfment of erythrocytes by hepatic macrophages may lead to the accumulation of iron derived from hemoglobin in liver and play a role in triggering the generation of oxidative stress in the disease course.

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We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.

Purpose Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL). Methods The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks. Results Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis. HPCs formed proliferating bile ductules and were scattered in periportal connective tissue. We distinguished 4 main types of HPCs: 0, I, II (bile duct-like cells; most common), and III (hepatocyte-like cells). We observed, very seldom presented in literature, cellular interactions between HPCs and adjacent NPCs, especially commonly found transitional hepatic stellate cells (T-HSCs) and Kupffer cells/macrophages. We showed the phenomenon of penetration of the basement membrane of proliferating bile ductules by cytoplasmic processes sent by T-HSCs and the formation of direct cell-cell contact with ductular epithelial cells related to HPCs. Conclusions HPC proliferation induced by BDL evidently promotes portal fibrogenesis. Better understanding of the complex cellular interactions between HPCs and adjacent NPCs, especially T-HSCs, may help develop antifibrotic therapies in the future.

No abstract

Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF -1a) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1a, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1a correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer.

The pathogenesis of autoimmune hepatitis (AIH) is poorly understood. Up to now, little is known of the involvement of liver sinusoidal endothelial cells (LSECs), accounting for approximately 40% of nonparenchymal hepatic cells, in AIH morphogenesis in pediatric patients. The study objective was ultrastructural analysis of LSECs from pretreatment biopsies of 19 children, aged 4-17 years (14 girls), with clinically and histologically diagnosed AIH. Our study is the first to describe alterations in LSECs, from swelling to necrosis, demonstrating their important role in the morphogenesis and progression of pediatric AIH. Frequently damage to LSECs coexisted with significantly activated Kupffer cells, fibrogenesis and fibrosis, but not cirrhosis, accompanied by the appearance of transitional hepatic stellate cells. Interestingly, even though in half of the AIH children the sinusoidal vessels were found to undergo transformation of discontinuous into continuous endothelium showing features of defenestration, the true basement membrane did not form underneath. The fact that the basement membrane is not formed, even when LSECs are markedly damaged, may seem to indicate some regenerative capacities of these cells and lesion reversibility.