Electron microscopic alterations in intermediate hepatocyte-like cells in children with chronic hepatitis B: the first report in pediatric patients

Łotowska, Joanna Maria; Sobaniec-Łotowska, M; Lebensztejn, Dariusz Marek

doi:10.1097/meg.0b013e32832e2c09

Cited by 5 publications

(10 citation statements)

References 44 publications

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“…The current study is a continuation of our earlier ultrastructural research conducted by means of TEM in pediatric AIH [4,11] and also of similar submicroscopic observations of the population of LPCs in other chronic liver diseases in children [37][38][39][40] and in the experimental model of biliary fibrosis [25].…”

Section: Introductionsupporting

confidence: 57%

Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease

Łotowska

Sobaniec-Łotowska

Sobaniec

2021

Cells

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Considering that the heterogenic population of a hepatic progenitor cell line (HPCL) can play a vital role in autoimmune hepatitis (AIH), we decided to conduct pioneering retrospective evaluation of these cells in pediatric AIH by means of transmission electron microscopy (TEM). The aim of the study was to assess the ultrastructure of the HPCL in children with untreated AIH. Ultrastructural analysis of the HPCL population, preceded by immunohistochemical staining for cytokeratin 7 (CK7), was performed using pretreatment liver biopsies from 23 children with clinicopathologically diagnosed AIH. Immunohistochemical assessment for CK7 allowed detection of proliferating immature epithelial cells differentiating towards periportal and intralobular intermediate hepatocytes without marked formation of ductular reactions in AIH children. Using TEM, we distinguished three morphological types of HPCs: I—the most undifferentiated progenitor cells; III—intermediate hepatocyte-like cells; II—intermediate bile duct cells. Most frequent were the cells differentiating towards hepatocytes, most rare—those differentiating towards cholangiocytes. The results indicate that an HPCL may be an important source of hepatocyte regeneration. Ultrastructural analyses of the HPCL population, combined with immunohistochemistry for CK7, might be a useful tool to evaluate liver cell regeneration, including fibrogenesis, and may help better understand the morphological pattern of the disease, in pediatric AIH. Frequent appearance of an HPCL in the vicinity of fibrotic foci, often accompanied by hyperactive Kupffer cells and transitional hepatic stellate cells, may indicate their significant involvement in liver fibrogenesis.

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Section: Introductionsupporting

confidence: 57%

Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease

Łotowska

Sobaniec-Łotowska

Sobaniec

2021

Cells

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“…Among the analyzed subpopulations of HPCs, the hepatocyte-like cells, that is, type III cells, were found to be most involved in the process of hepatic fibrosis in the abovementioned diseases in children [24–26, 38]. …”

Section: Discussionmentioning

confidence: 99%

“…The blocks were then used to prepare ultrathin sections (60–70 nm thick), which were placed on grids, contrasted with uranyl acetate and lead citrate, examined using an Opton EM 900 transmission electron microscope (Zeiss, Oberkochen, Germany), and photographed with TRS camera (CCD camera for TEM 2K inside). This processing procedure had been used in our earlier ultrastructural investigations of liver in children [25, 26, 38]. …”

Section: Methodsmentioning

confidence: 99%

“…Thus, transmission electron microscopic (TEM) analysis is thought to be the most reliable and valuable, although extremely laborious, method of morphological identification of HPCs and its various cell types [14, 22, 24–26]. …”

Section: Introductionmentioning

confidence: 99%

“…The study is a continuation of our morphological and clinical research, with a focus on the ultrastructural analysis of the role of hepatic progenitor/oval cells in fibrogenesis in various chronic liver diseases in pediatric patients [24–26], and experimental investigation of the fibroductular reaction in the same model of liver fibrosis [35]. …”

Section: Introductionmentioning

confidence: 99%

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Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis

Łotowska

Sobaniec-Łotowska

Lebensztejn

et al. 2017

Gastroenterology Research and Practice

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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.

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Mitochondrial changes associated with viral infectious diseases in the paediatric population

Romero-Cordero

Noguera-Julián

Cardellach

et al. 2021

Reviews in Medical Virology

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Summary Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization reports. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins into the complexes of the electron transport chain; (ii) impact on mitochondrial genome (depletion, deletions and point mutations) and mitochondrial dynamics (fusion and fission); (iii) membrane potential impairment; (iv) apoptotic regulation; and (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with considerable impact on the quality of life of the children and could even cause death. Herein, we use a systematic review to explore the association between mitochondrial alterations in paediatric infections including human immunodeficiency virus, cytomegalovirus, herpes viruses, various forms of hepatitis, adenovirus, T‐cell lymphotropic virus and influenza. We analyse how these paediatric viral infectious processes may cause mitochondrial deterioration in this especially vulnerable population, with consideration for the principal aspects of research and diagnosis leading to improved disease understanding, management and surveillance.

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Electron microscopic alterations in intermediate hepatocyte-like cells in children with chronic hepatitis B: the first report in pediatric patients

Abstract: Our study seems to suggest that chronic HBV infection, lasting from childhood and coexisting with intensive fibrosis may, with the involvement of other carcinogenic factors, promote degenerating IHCs towards neoplastic transformation in adulthood.

Cited by 5 publications

References 44 publications

Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease

Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease

Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis

Mitochondrial changes associated with viral infectious diseases in the paediatric population

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