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Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease

OBJECTIVES: Soluble CD163 (sCD163), a marker of Kupffer cell activation detectable in serum, correlates with inflammation and fibrosis in chronic viral hepatitis, but its role in nonalcoholic fatty liver disease is unknown. We hypothesized that sCD163 would correlate with nonalcoholic fatty liver di...

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Autores principales: Mueller, Jessica L, Feeney, Eoin R, Zheng, Hui, Misdraji, Joseph, Kruger, Annie J, Alatrakchi, Nadia, King, Lindsay Y, Gelrud, Louis, Corey, Kathleen E, Chung, Raymond T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816035/
https://www.ncbi.nlm.nih.gov/pubmed/26448455
http://dx.doi.org/10.1038/ctg.2015.36
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author Mueller, Jessica L
Feeney, Eoin R
Zheng, Hui
Misdraji, Joseph
Kruger, Annie J
Alatrakchi, Nadia
King, Lindsay Y
Gelrud, Louis
Corey, Kathleen E
Chung, Raymond T
author_facet Mueller, Jessica L
Feeney, Eoin R
Zheng, Hui
Misdraji, Joseph
Kruger, Annie J
Alatrakchi, Nadia
King, Lindsay Y
Gelrud, Louis
Corey, Kathleen E
Chung, Raymond T
author_sort Mueller, Jessica L
collection PubMed
description OBJECTIVES: Soluble CD163 (sCD163), a marker of Kupffer cell activation detectable in serum, correlates with inflammation and fibrosis in chronic viral hepatitis, but its role in nonalcoholic fatty liver disease is unknown. We hypothesized that sCD163 would correlate with nonalcoholic fatty liver disease activity and fibrosis. METHODS: Liver biopsies and serum were obtained from 145 obese subjects undergoing gastric bypass surgery. Subjects were divided into four groups based on fibrosis stage and nonalcoholic fatty liver disease activity score (NAS); Group 1: F0, NAS=0; Group 2: F<2, 0<NAS<5; Group 3: NAS≥5, F<3; or Group 4: F≥3, any NAS. Serum sCD163 and the monocyte/macrophage marker sCD14 were measured by enzyme-linked immunosorbent assay. Relationships between sCD163, sCD14, fibrosis stage, and NAS were examined. Area under the receiver operating charateristic for the diagnosis of nonalcoholic steatohepatitis based on the Clinical Research Network definition was calculated. RESULTS: sCD163 increased with progressive liver histology, with lowest values in normal histology and highest levels in those with nonalcoholic steatohepatitis and advanced fibrosis (Group 1: 552 ng/ml, Group 2: 721 ng/ml, Group 3: 803 ng/ml, and Group 4:1,031; P=0.001). sCD14 also differed significantly across groups (Group 1: 1,877 ng/ml, Group 2: 1632 ng/ml, Group 3: 1,706 ng/ml, and Group 4: 2111; P=0.008, respectively). sCD163 correlated with steatosis grade (P<0.001), lobular inflammation (P=0.033), and hepatocyte ballooning (P<0.001). In a multivariable ordered logistic regression model, there was a significant association between every 100 ng/ml increase in sCD163 and higher fibrosis stage, with an odds ratio of 1.16 (95% confidence interval 1.02–1.31), P=0.020. The odds ratios of the association between every 100 ng/ml increase in sCD163 and higher NAS was 1.17 (95% confidence interval 1.04–1.32), P=0.010. A sCD163-based predictive score demonstrated an area under the receiver operating charateristic of 0.70 (95% confidence interval: 0.58–0.82) for the diagnosis of nonalcoholic steatohepatitis. Soluble CD14 did not correlate with fibrosis stage or NAS. CONCLUSIONS: In obese subjects, serum sCD163, but not sCD14, correlated with fibrosis stage and NAS. These data support a role for activated Kupffer cells in the pathogenesis of nonalcoholic steatohepatitis and fibrosis, and suggest potential clinical utility for assessment of sCD163 levels.
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spelling pubmed-48160352016-04-13 Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Mueller, Jessica L Feeney, Eoin R Zheng, Hui Misdraji, Joseph Kruger, Annie J Alatrakchi, Nadia King, Lindsay Y Gelrud, Louis Corey, Kathleen E Chung, Raymond T Clin Transl Gastroenterol Original Contributions OBJECTIVES: Soluble CD163 (sCD163), a marker of Kupffer cell activation detectable in serum, correlates with inflammation and fibrosis in chronic viral hepatitis, but its role in nonalcoholic fatty liver disease is unknown. We hypothesized that sCD163 would correlate with nonalcoholic fatty liver disease activity and fibrosis. METHODS: Liver biopsies and serum were obtained from 145 obese subjects undergoing gastric bypass surgery. Subjects were divided into four groups based on fibrosis stage and nonalcoholic fatty liver disease activity score (NAS); Group 1: F0, NAS=0; Group 2: F<2, 0<NAS<5; Group 3: NAS≥5, F<3; or Group 4: F≥3, any NAS. Serum sCD163 and the monocyte/macrophage marker sCD14 were measured by enzyme-linked immunosorbent assay. Relationships between sCD163, sCD14, fibrosis stage, and NAS were examined. Area under the receiver operating charateristic for the diagnosis of nonalcoholic steatohepatitis based on the Clinical Research Network definition was calculated. RESULTS: sCD163 increased with progressive liver histology, with lowest values in normal histology and highest levels in those with nonalcoholic steatohepatitis and advanced fibrosis (Group 1: 552 ng/ml, Group 2: 721 ng/ml, Group 3: 803 ng/ml, and Group 4:1,031; P=0.001). sCD14 also differed significantly across groups (Group 1: 1,877 ng/ml, Group 2: 1632 ng/ml, Group 3: 1,706 ng/ml, and Group 4: 2111; P=0.008, respectively). sCD163 correlated with steatosis grade (P<0.001), lobular inflammation (P=0.033), and hepatocyte ballooning (P<0.001). In a multivariable ordered logistic regression model, there was a significant association between every 100 ng/ml increase in sCD163 and higher fibrosis stage, with an odds ratio of 1.16 (95% confidence interval 1.02–1.31), P=0.020. The odds ratios of the association between every 100 ng/ml increase in sCD163 and higher NAS was 1.17 (95% confidence interval 1.04–1.32), P=0.010. A sCD163-based predictive score demonstrated an area under the receiver operating charateristic of 0.70 (95% confidence interval: 0.58–0.82) for the diagnosis of nonalcoholic steatohepatitis. Soluble CD14 did not correlate with fibrosis stage or NAS. CONCLUSIONS: In obese subjects, serum sCD163, but not sCD14, correlated with fibrosis stage and NAS. These data support a role for activated Kupffer cells in the pathogenesis of nonalcoholic steatohepatitis and fibrosis, and suggest potential clinical utility for assessment of sCD163 levels. Nature Publishing Group 2015-10 2015-10-08 /pmc/articles/PMC4816035/ /pubmed/26448455 http://dx.doi.org/10.1038/ctg.2015.36 Text en Copyright © 2015 American College of Gastroenterology http://creativecommons.org/licenses/by-nc-nd/4.0/ Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Contributions
Mueller, Jessica L
Feeney, Eoin R
Zheng, Hui
Misdraji, Joseph
Kruger, Annie J
Alatrakchi, Nadia
King, Lindsay Y
Gelrud, Louis
Corey, Kathleen E
Chung, Raymond T
Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title_full Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title_fullStr Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title_full_unstemmed Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title_short Circulating Soluble CD163 is Associated with Steatohepatitis and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
title_sort circulating soluble cd163 is associated with steatohepatitis and advanced fibrosis in nonalcoholic fatty liver disease
topic Original Contributions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816035/
https://www.ncbi.nlm.nih.gov/pubmed/26448455
http://dx.doi.org/10.1038/ctg.2015.36
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