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

Skytthe, Maria Kløjgaard; Pedersen, Felix Boel; Wernberg, Charlotte Wilhelmina; Indira Chandran, Vineesh; Krag, Aleksander; Di Caterino, Tina; Mandacaru, Samuel Coelho; Blagoev, Blagoy; Lauridsen, Mette Munk; Detlefsen, Sönke; Graversen, Jonas Heilskov; Moestrup, Søren Kragh

Skytthe, Maria Kløjgaard; Pedersen, Felix Boel; Wernberg, Charlotte Wilhelmina; Indira Chandran, Vineesh; Krag, Aleksander; Di Caterino, Tina; Mandacaru, Samuel Coelho; Blagoev, Blagoy; Lauridsen, Mette Munk; Detlefsen, Sönke; Graversen, Jonas Heilskov; Moestrup, Søren Kragh.

Afiliação

Skytthe MK; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Pedersen FB; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Wernberg CW; Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, Denmark.
Indira Chandran V; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Krag A; Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, Denmark.
Di Caterino T; Department of Gastroenterology and Hepatology, Centre for Liver Research, Odense University Hospital, Odense, Denmark.
Mandacaru SC; Department of Pathology, Odense University Hospital, Odense Denmark.
Blagoev B; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Lauridsen MM; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Detlefsen S; Department of Gastroenterology and Hepatology, Liver Research Group, University Hospital of South Denmark, Esbjerg, Denmark.
Graversen JH; Department of Pathology, Odense University Hospital, Odense Denmark.
Moestrup SK; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Gastro Hep Adv ; 2(5): 711-720, 2023.

Article em En | MEDLINE | ID: mdl-39129874

ABSTRACT

ABSTRACT

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).