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Thomas Damgaard Sandahl

High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study

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High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study. / Björklund, Jessica; Laursen, Tea Lund; Sandahl, Thomas Damgaard et al.

In: Orphanet Journal of Rare Diseases, Vol. 13, No. 169, 21.09.2018, p. 1-6.

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@article{1eafbb9e20a244d7a8e118faec8bf0fd,
title = "High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study",
abstract = "Background: Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson{\textquoteright}s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of soluble (s)CD163, metabolic liver function by the galactose elimination capacity (GEC), and fibrosis by Fibroscan. We investigated the associations between sCD163, selected inflammatory cytokines, GEC, and liver fibrosis in Danish WD patients. Methods: In a cross-sectional design, we studied 29 stable and well-treated patients (male/female15/14) with a median age of 35 years (IQR 24-50). P-sCD163 and cytokines were measured by ELISA. The GEC was measured by intra-venous galactose loading. Results: The median P-sCD163 value at 2.96 mg/L (1.97-3.93) was high in the normal range (0.7-3.9) and seven patients (24%) had a value above the upper normal value. sCD163 correlated with TNF-α, IL-6 and IL-8 (rho> 0.50, p < 0.005). A higher sCD163 value was closely associated with a lower GEC (rho = − 0.51, p = 0.02). sCD163 was not related to the liver fibrosis indices. Conclusions: Stable WD patients showed various degrees of Kupffer cell activation which was accompanied by loss of metabolic liver function. Neither activation nor liver function was related to liver fibrosis. The findings suggest that in WD inflammatory Kupffer cell activation may be involved in the loss of liver function over time. sCD163 may serve as a non-invasive biomarker of loss of liver function in WD, which the degree of fibrosis evidently may not. This study is registered at clinical trials with name: “sCD163 and sMR in Wilsons Disease - Associations With Disease Severity and Fibrosis”, NCT02702765. Date of registration: 26.02.16. Date of enrolment of the first participant to the trial: 17.03.16. ULR: https://clinicaltrials.gov/ct2/show/NCT02702765 .",
keywords = "Liver, Macrophages, Metabolic liver function, sCD163, Wilson disease",
author = "Jessica Bj{\"o}rklund and Laursen, {Tea Lund} and Sandahl, {Thomas Damgaard} and M{\o}ller, {Holger Jon} and Hendrik Vilstrup and Peter Ott and Henning Gr{\o}nb{\ae}k",
year = "2018",
month = sep,
day = "21",
doi = "10.1186/s13023-018-0910-7",
language = "English",
volume = "13",
pages = "1--6",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central",
number = "169",

}

RIS

TY - JOUR

T1 - High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study

AU - Björklund, Jessica

AU - Laursen, Tea Lund

AU - Sandahl, Thomas Damgaard

AU - Møller, Holger Jon

AU - Vilstrup, Hendrik

AU - Ott, Peter

AU - Grønbæk, Henning

PY - 2018/9/21

Y1 - 2018/9/21

N2 - Background: Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson’s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of soluble (s)CD163, metabolic liver function by the galactose elimination capacity (GEC), and fibrosis by Fibroscan. We investigated the associations between sCD163, selected inflammatory cytokines, GEC, and liver fibrosis in Danish WD patients. Methods: In a cross-sectional design, we studied 29 stable and well-treated patients (male/female15/14) with a median age of 35 years (IQR 24-50). P-sCD163 and cytokines were measured by ELISA. The GEC was measured by intra-venous galactose loading. Results: The median P-sCD163 value at 2.96 mg/L (1.97-3.93) was high in the normal range (0.7-3.9) and seven patients (24%) had a value above the upper normal value. sCD163 correlated with TNF-α, IL-6 and IL-8 (rho> 0.50, p < 0.005). A higher sCD163 value was closely associated with a lower GEC (rho = − 0.51, p = 0.02). sCD163 was not related to the liver fibrosis indices. Conclusions: Stable WD patients showed various degrees of Kupffer cell activation which was accompanied by loss of metabolic liver function. Neither activation nor liver function was related to liver fibrosis. The findings suggest that in WD inflammatory Kupffer cell activation may be involved in the loss of liver function over time. sCD163 may serve as a non-invasive biomarker of loss of liver function in WD, which the degree of fibrosis evidently may not. This study is registered at clinical trials with name: “sCD163 and sMR in Wilsons Disease - Associations With Disease Severity and Fibrosis”, NCT02702765. Date of registration: 26.02.16. Date of enrolment of the first participant to the trial: 17.03.16. ULR: https://clinicaltrials.gov/ct2/show/NCT02702765 .

AB - Background: Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson’s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of soluble (s)CD163, metabolic liver function by the galactose elimination capacity (GEC), and fibrosis by Fibroscan. We investigated the associations between sCD163, selected inflammatory cytokines, GEC, and liver fibrosis in Danish WD patients. Methods: In a cross-sectional design, we studied 29 stable and well-treated patients (male/female15/14) with a median age of 35 years (IQR 24-50). P-sCD163 and cytokines were measured by ELISA. The GEC was measured by intra-venous galactose loading. Results: The median P-sCD163 value at 2.96 mg/L (1.97-3.93) was high in the normal range (0.7-3.9) and seven patients (24%) had a value above the upper normal value. sCD163 correlated with TNF-α, IL-6 and IL-8 (rho> 0.50, p < 0.005). A higher sCD163 value was closely associated with a lower GEC (rho = − 0.51, p = 0.02). sCD163 was not related to the liver fibrosis indices. Conclusions: Stable WD patients showed various degrees of Kupffer cell activation which was accompanied by loss of metabolic liver function. Neither activation nor liver function was related to liver fibrosis. The findings suggest that in WD inflammatory Kupffer cell activation may be involved in the loss of liver function over time. sCD163 may serve as a non-invasive biomarker of loss of liver function in WD, which the degree of fibrosis evidently may not. This study is registered at clinical trials with name: “sCD163 and sMR in Wilsons Disease - Associations With Disease Severity and Fibrosis”, NCT02702765. Date of registration: 26.02.16. Date of enrolment of the first participant to the trial: 17.03.16. ULR: https://clinicaltrials.gov/ct2/show/NCT02702765 .

KW - Liver

KW - Macrophages

KW - Metabolic liver function

KW - sCD163

KW - Wilson disease

UR - http://www.scopus.com/inward/record.url?scp=85053695121&partnerID=8YFLogxK

U2 - 10.1186/s13023-018-0910-7

DO - 10.1186/s13023-018-0910-7

M3 - Journal article

C2 - 30241550

AN - SCOPUS:85053695121

VL - 13

SP - 1

EP - 6

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 169

ER -