Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163

Background and Aims: Macrophages play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). In this study, we investigated the hepatic expression of the macrophage scavenger receptor CD163 and the plasma level of...

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Main Authors: Maria Kløjgaard Skytthe, Felix Boel Pedersen, Charlotte Wilhelmina Wernberg, Vineesh Indira Chandran, Aleksander Krag, Tina Di Caterino, Samuel Coelho Mandacaru, Blagoy Blagoev, Mette Munk Lauridsen, Sönke Detlefsen, Jonas Heilskov Graversen, Søren Kragh Moestrup
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Gastro Hep Advances
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772572323000419
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author Maria Kløjgaard Skytthe
Felix Boel Pedersen
Charlotte Wilhelmina Wernberg
Vineesh Indira Chandran
Aleksander Krag
Tina Di Caterino
Samuel Coelho Mandacaru
Blagoy Blagoev
Mette Munk Lauridsen
Sönke Detlefsen
Jonas Heilskov Graversen
Søren Kragh Moestrup
author_facet Maria Kløjgaard Skytthe
Felix Boel Pedersen
Charlotte Wilhelmina Wernberg
Vineesh Indira Chandran
Aleksander Krag
Tina Di Caterino
Samuel Coelho Mandacaru
Blagoy Blagoev
Mette Munk Lauridsen
Sönke Detlefsen
Jonas Heilskov Graversen
Søren Kragh Moestrup
author_sort Maria Kløjgaard Skytthe
collection DOAJ
description Background and Aims: Macrophages play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). In this study, we investigated the hepatic expression of the macrophage scavenger receptor CD163 and the plasma level of its shed soluble form (sCD163) in patients with obesity and NASH, non-NASH NAFLD (NAFL), or healthy livers (no NAFLD). Methods: Paired liver biopsies and plasma samples were collected from 61 patients with obesity (body mass index ≥35). Hepatic expression of CD163 was analyzed by immunohistochemistry and data-independent acquisition mass spectrometry, whilst plasma levels of sCD163 were determined by enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. NAFLD stage and activity were assessed using the Kleiner fibrosis and NASH Clinical Research Network (NAS-CRN) scoring system. Results: sCD163 turned out as a promising predictor of NASH with an area under the receiver-operating characteristic curve of 0.78 [0.65;0.92] (P = .0008). sCD163 increased with more severe NAFLD both in univariate (odds ratio [OR] = 3.31[1.80;6.11], P < .001) and multivariable ordinal logistic regression adjusting for NAFLD risk factors (OR = 2.02 [1.03;3.97], P = .042). On the other hand, hepatic expression of CD163 was negatively associated with more severe NAFLD in univariate ordinal logistic regression determined by immunohistochemistry (OR = 0.91[0.84;0.98], P = .015) and proteomics (OR = 0.13[0.02;0.80], P = .028). Taking NAFLD risk factors into account, hepatic expression of CD163 was only associated with the fibrosis stage (OR = 0.01 [0.0003;0.21], P = .004). Accordingly, hepatic CD163 surface expression and sCD163 were negatively correlated (rho = −0.478, P = .0001). Conclusion: An increased plasma sCD163 and a concurrent decreased hepatic expression of CD163 are strongly associated with NAFLD in obese patients.
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spelling doaj.art-74d5897d531b4a1f86e9c429e3094ae42023-07-19T04:24:08ZengElsevierGastro Hep Advances2772-57232023-01-0125711720Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163Maria Kløjgaard Skytthe0Felix Boel Pedersen1Charlotte Wilhelmina Wernberg2Vineesh Indira Chandran3Aleksander Krag4Tina Di Caterino5Samuel Coelho Mandacaru6Blagoy Blagoev7Mette Munk Lauridsen8Sönke Detlefsen9Jonas Heilskov Graversen10Søren Kragh Moestrup11Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Correspondence: Address correspondence to: Maria Kløjgaard Skytthe, MSc, University of Southern Denmark, J. B. Winsløwsvej 25, 5230 Odense, Denmark.Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DenmarkDepartment of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkDepartment of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, Denmark; Department of Gastroenterology and Hepatology, Centre for Liver Research, Odense University Hospital, Odense, DenmarkDepartment of Pathology, Odense University Hospital, Odense DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DenmarkDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DenmarkDepartment of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, DenmarkDepartment of Pathology, Odense University Hospital, Odense Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Biomedicine, Aarhus University, Aarhus Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, DenmarkBackground and Aims: Macrophages play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). In this study, we investigated the hepatic expression of the macrophage scavenger receptor CD163 and the plasma level of its shed soluble form (sCD163) in patients with obesity and NASH, non-NASH NAFLD (NAFL), or healthy livers (no NAFLD). Methods: Paired liver biopsies and plasma samples were collected from 61 patients with obesity (body mass index ≥35). Hepatic expression of CD163 was analyzed by immunohistochemistry and data-independent acquisition mass spectrometry, whilst plasma levels of sCD163 were determined by enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. NAFLD stage and activity were assessed using the Kleiner fibrosis and NASH Clinical Research Network (NAS-CRN) scoring system. Results: sCD163 turned out as a promising predictor of NASH with an area under the receiver-operating characteristic curve of 0.78 [0.65;0.92] (P = .0008). sCD163 increased with more severe NAFLD both in univariate (odds ratio [OR] = 3.31[1.80;6.11], P < .001) and multivariable ordinal logistic regression adjusting for NAFLD risk factors (OR = 2.02 [1.03;3.97], P = .042). On the other hand, hepatic expression of CD163 was negatively associated with more severe NAFLD in univariate ordinal logistic regression determined by immunohistochemistry (OR = 0.91[0.84;0.98], P = .015) and proteomics (OR = 0.13[0.02;0.80], P = .028). Taking NAFLD risk factors into account, hepatic expression of CD163 was only associated with the fibrosis stage (OR = 0.01 [0.0003;0.21], P = .004). Accordingly, hepatic CD163 surface expression and sCD163 were negatively correlated (rho = −0.478, P = .0001). Conclusion: An increased plasma sCD163 and a concurrent decreased hepatic expression of CD163 are strongly associated with NAFLD in obese patients.http://www.sciencedirect.com/science/article/pii/S2772572323000419CD163NASHNAFLDImmunohistochemistryProteomicsTranslational
spellingShingle Maria Kløjgaard Skytthe
Felix Boel Pedersen
Charlotte Wilhelmina Wernberg
Vineesh Indira Chandran
Aleksander Krag
Tina Di Caterino
Samuel Coelho Mandacaru
Blagoy Blagoev
Mette Munk Lauridsen
Sönke Detlefsen
Jonas Heilskov Graversen
Søren Kragh Moestrup
Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
Gastro Hep Advances
CD163
NASH
NAFLD
Immunohistochemistry
Proteomics
Translational
title Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
title_full Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
title_fullStr Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
title_full_unstemmed Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
title_short Obese Patients With Nonalcoholic Fatty Liver Disease Have an Increase in Soluble Plasma CD163 and a Concurrent Decrease in Hepatic Expression of CD163
title_sort obese patients with nonalcoholic fatty liver disease have an increase in soluble plasma cd163 and a concurrent decrease in hepatic expression of cd163
topic CD163
NASH
NAFLD
Immunohistochemistry
Proteomics
Translational
url http://www.sciencedirect.com/science/article/pii/S2772572323000419
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