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<a href="http://doi.org/10.14309/01.ajg.0000706532.82398.af" target="_blank" rel="noreferrer noopener">http://doi.org/10.14309/01.ajg.0000706532.82398.af</a>
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Pages
S564-S565
Issue
S
Volume
115
ISSN
0002-9270
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Update Year & Number
February 2021 List
NEOMED College
NEOMED College of Pharmacy
NEOMED Department
Department of Pharmaceutical Sciences
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Title
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Role of Markers of Heavy Metal Metabolism in Identification of Hepatic Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)
Date
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2020
2020-10
Subject
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Oxidative stress; hepatic fibrosis; non-alcoholic fatty liver disease; Heavy Metals; non-alcoholic steatohepatitis (NASH)
Creator
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Aggarwal Manik;Mitchell B;Singh AD;Kasumov T;McCullough A
Description
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INTRODUCTION: Fibrosis & nonalcoholic steatohepatitis (NASH) are important predictors of long term prognosis in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress (OS) has been shown to play a central role in progression of NAFLD, & changes in proteins associated with metal homeostasis may exacerbate OS. We investigated relationship of proteins related to transition metal metabolism with fibrosis in NAFLD. METHODS: Adult patients (>18y) who underwent liver biopsy for clinically suspected NAFLD at our institution were included. We retrospectively collected serum levels of ceruloplasmin (Cp), ferritin, iron, & transferrin saturation (Tsat) within 3 months of liver biopsy & calculated Cp/Tsat ratio (CT ratio) & Cp/Ferritin ratio (CF ratio). Histologic features were scored by an experienced pathologist using Non-alcoholic Steatohepatitis Clinical Research Network criteria. Fibrosis was staged as (0 - 4). Independent T test were used to compare the means & receiver operating characteristics (ROC) curves were plotted for assessing area under curve (AUC), sensitivity (Sn) & specificity (Sp). RESULTS: 174 patients were included in final analysis. The mean age of subjects was 48 y. Baseline features are depicted in Table 1. Biopsy proven NASH was seen in 61.5% of liver biopsies. No fibrosis was seen in 29.3% of liver biopsies & Stage 1, 2,3& 4 fibrosis were seen in 29.9%, 10.9%, 14.3% & 15.55% of samples. Mean Tsat was significantly higher (24.41% v/s 38.27%, P < 0.0001) & Cp (mg/dl) (27.82 v/s 24.91, P = 0.03) significantly lower between patients with advanced fibrosis (AF) (3-4) v/s early fibrosis (EF) (0-2). The mean CT ratio was also higher in patients with EF v/s AF (1.54 v/s 1.02, P = 0.01). The mean Tsat of patients with fibrosis v/s without fibrosis was higher (31.4% v/s 21.57% P < 0.005) however mean Cp (mg/dl) values were not significantly different (27.88 v/s 27.58, P = 0.42). The ROC curves show CF ratio (Figure 1) at a cut off of 0.10 had AUC = 0.61 (Sn = 70%, Sp = 52% P = 0.01) to detect any fibrosis & CT ratio (Figure 2) at a cut off 0.86 had AUC = 0.65 (Sn = 69%, Sp = 50% P = 0.002) for differentiating EF v/s AF. CONCLUSION: Our data reveals changes in ceruloplasmin: transferrin system, which decreases the content of toxic ions of Fe2+ in NAFLD. Tsat, Cp, CF ratio & CT ratio are useful non-invasive biomarkers in identifying NAFLD patients with fibrosis. Markers of heavy metal metabolism can spare patients from liver biopsies & can be potential therapeutic targets in future.
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<a href="http://doi.org/10.14309/01.ajg.0000706532.82398.af" target="_blank" rel="noreferrer noopener">10.14309/01.ajg.0000706532.82398.af</a>
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journalArticle
Publisher
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American Journal Of Gastroenterology
2020
Aggarwal Manik
American Journal of Gastroenterology
Department of Pharmaceutical Sciences
February 2021 List
Heavy Metals
hepatic fibrosis
journalArticle
Kasumov T
McCullough A
Mitchell B
NEOMED College of Pharmacy
non-alcoholic steatohepatitis (NASH)
Non-alcoholic Fatty Liver Disease
Oxidative Stress
Singh AD
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep.30513" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.30513</a>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Deficiency of both farnesoid X receptor and Takeda G protein-coupled receptor 5 exacerbated liver fibrosis in mice.
Publisher
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Hepatology (Baltimore, Md.)
Date
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2019
2019-01
Subject
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Bile acid metabolism; FXR; gene expression; hepatic fibrosis; TGR5
Creator
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Ferrell Jessica M; Pathak Preeti; Boehme Shannon; Gilliland Tricia; Chiang John Y L
Description
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Activation of the nuclear bile acid receptor farnesoid X receptor (FXR) protects against hepatic inflammation and injury, while Takeda G protein-coupled receptor 5 (TGR5) promotes adipose tissue browning and energy metabolism. Here, we examined the physiological and metabolic effects of the deficiency of these two bile acid receptors on hepatic metabolism and injury in mice. Fxr/Tgr5 double knockout mice (DKO) were generated for metabolic phenotyping. Male DKO mice fed chow diet had reduced liver lipid levels but increased serum cholesterol levels. Liver Cyp7a1 activity and Cyp8b1 mRNA levels were induced, while ileum FXR target genes were suppressed in DKO mice compared to WT mice. Bile acid pool size was increased in DKO mice, with increased tauro-cholic acid and decreased tauro-muricholic acids. RNA sequencing analysis of the liver transcriptome revealed that bile acid synthesis and fibrosis gene expression levels are increased in chow-fed DKO mice compared to WT mice and the top regulated pathways are involved in steroid/cholesterol biosynthesis, liver cirrhosis and connective tissue disease. Cholestyramine treatment further induced Cyp7a1 mRNA and protein in DKO mice, and increased bile acid pool size, while cholic acid also induced Cyp7a1 in DKO mice, suggesting impaired bile acid feedback regulation. Western diet containing 0.2% cholesterol increased oxidative stress and markers of liver fibrosis, but not hepatic steatosis in DKO mice. In conclusion, FXR and TGR5 play critical roles in protecting the liver from inflammation and fibrosis. Deficiency of both of these bile acid receptors in mice increased cholic acid synthesis and bile acid pool, liver fibrosis and inflammation. FXR and TGR5 double knockout mice may be a novel mouse model for liver fibrosis. This article is protected by copyright. All rights reserved.
Identifier
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<a href="http://doi.org/10.1002/hep.30513" target="_blank" rel="noreferrer noopener">10.1002/hep.30513</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2019
Bile acid metabolism
Boehme Shannon
Chiang John Y L
Department of Integrative Medical Sciences
Ferrell Jessica M
FXR
Gene Expression
Gilliland Tricia
hepatic fibrosis
Hepatology (Baltimore, Md.)
NEOMED College of Medicine
Pathak Preeti
TGR5