| Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C. | |
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MedLine Citation:
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PMID: 20966027 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To study the mechanism(s) linking insulin resistance (IR) to hepatic fibrosis and the role of the epithelial component in tissue repair and fibrosis in chronic hepatitis C (CHC). DESIGN: Prospective observational study. SETTING: Tertiary care academic centre. PATIENTS: 78 consecutive patients with CHC. MAIN OUTCOME MEASURES: IR, calculated by the oral glucose insulin sensitivity during oral glucose tolerance test; necroinflammatory activity and fibrosis, defined according to Ishak's score; steatosis, graded as 0 (<5% of hepatocytes), 1 (5-33%), 2 (33-66%) and 3 (>66%). To evaluate the role of the epithelial component in tissue repair and fibrosis, the expansion of the ductular reaction (DR) was calculated by keratin-7 (CK7) morphometry. Nuclear expression of Snail, downregulation of E-cadherin and expression of fibroblast specific protein-1 (FSP1) and vimentin by CK7-positive cells were used as markers of epithelial-mesenchymal transition in DR elements. RESULTS: IR, the degree of necroinflammation and expansion of the DR (stratified as reactive ductular cells (RDCs), hepatic progenitor cells and intermediate hepatobiliary cells according to morphological criteria) were all associated with the stage of fibrosis. Nuclear Snail expression, E-cadherin downregulation and vimentin upregulation were observed in RDCs. By dual immunofluorescence for CK7 and FSP1, the number of RDCs undergoing epithelial-mesenchymal transition progressively increased together with the necroinflammatory score. By multivariate analysis, total inflammation and insulin resistance were the only factors significantly predicting the presence of advanced fibrosis (Ishak score ≥3) and the expansion of RDCs. CONCLUSION: This study indicates that IR is associated with the degree of necroinflammatory injury in CHC and contributes to hepatic fibrosis by stimulating the expansion of RDCs that express epithelial-mesenchymal transition markers. |
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Authors:
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Gianluca Svegliati-Baroni; Graziella Faraci; Luca Fabris; Stefania Saccomanno; Massimiliano Cadamuro; Irene Pierantonelli; Luciano Trozzi; Elisabetta Bugianesi; Maria Guido; Mario Strazzabosco; Antonio Benedetti; Giulio Marchesini |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-21 |
Journal Detail:
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Title: Gut Volume: 60 ISSN: 1468-3288 ISO Abbreviation: Gut Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-01-21 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 2985108R Medline TA: Gut Country: England |
Other Details:
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Languages: eng Pagination: 108-15 Citation Subset: AIM; IM |
Affiliation:
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Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy. g.svegliati@univpm.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anthropometry / methods Disease Progression Epithelial-Mesenchymal Transition / physiology* Female Glucose Tolerance Test / methods Hepatitis C, Chronic / complications, pathology*, physiopathology Humans Insulin Resistance / physiology* Liver / pathology* Liver Cirrhosis / pathology, physiopathology, virology Male Middle Aged Necrosis / physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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DK079005/DK/NIDDK NIH HHS; DK34989/DK/NIDDK NIH HHS; GGP09189//Telethon |
| Comments/Corrections | |
Comment In:
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Gut. 2011 Jan;60(1):1-2
[PMID:
21030525
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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