{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:23:36Z","timestamp":1792513416040,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":396,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Macrophages are involved in inflammation and liver fibrosis and soluble (s)CD163 is a specific marker of activated macrophages. We investigated associations between sCD163 and biochemical and histological parameters of inflammatory activity and fibrosis in 551 patients with chronic hepatitis C virus (HCV) and 203 patients with chronic hepatitis B virus (HBV) before antiviral treatment. Scheuer histological scores of activity and fibrosis were obtained. Clinical, biochemical, and metabolic parameters were recorded. We measured sCD163 by enzyme-linked immunosorbent assay (ELISA). Soluble CD163 was higher in patients with HCV compared to HBV (3.6 [interquartile range (IQR) 2.5-5.4] versus 2.4 [IQR 1.8-3.6] mg\/L, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). sCD163 was associated with fibrosis stages for both HCV (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.38-1.61) and HBV (OR 1.32, 95% CI: 1.17-1.49) patients, with highest levels in patients with advanced fibrosis and cirrhosis. sCD163 was a marker of fibrosis independent of other biochemical parameters and known risk factors. We created two novel sCD163-based fibrosis scores, CD163-HCV-FS and CD163-HBV-FS, which showed areas under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI: 0.74-0.83) and 0.71 (95% CI: 0.62-0.79), respectively, for significant fibrosis. Compared to existing fibrosis scores, CD163-HCV-FS was significantly superior to the aspartate aminotransferase (AST) to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis, but CD163-HBV-FS was not. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-HCV-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with HCV infection. (Hepatology 2014;60:521\u2013530)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.27129","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T10:03:52Z","timestamp":1394705032000},"page":"521-530","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":152,"title":["Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C"],"prefix":"10.1097","volume":"60","author":[{"given":"Konstantin","family":"Kazankov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger Jon","family":"M\u03c6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Martin","family":"Bibby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Vilstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Gr\u03c6nb\u00e6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-13-20250207","doi-asserted-by":"crossref","first-page":"245257","DOI":"10.1055\/s-0030-1255354","article-title":"Macrophages: master regulators of inflammation and fibrosis.","volume":"30","author":"Wynn","year":"2010","journal-title":"Semin Liver Dis"},{"key":"R2-13-20250207","doi-asserted-by":"crossref","first-page":"14171419","DOI":"10.1016\/j.jhep.2011.10.026","article-title":"Macrophages: central regulators of hepatic fibrogenesis and fibrosis resolution.","volume":"56","author":"Ramachandran","year":"2012","journal-title":"J Hepatol"},{"key":"R3-13-20250207","doi-asserted-by":"crossref","first-page":"10571064","DOI":"10.1007\/s10620-010-1395-y","article-title":"HCVrelated proteins activate Kupffer cells isolated from human liver tissues.","volume":"56","author":"Hosomura","year":"2011","journal-title":"Dig Dis Sci"},{"key":"R4-13-20250207","doi-asserted-by":"crossref","first-page":"305314","DOI":"10.1053\/j.gastro.2009.09.009","article-title":"Hepatitis C virus core protein subverts the antiviral activities of human Kupffer cells.","volume":"138","author":"Tu","year":"2010","journal-title":"Gastroenterology"},{"key":"R5-13-20250207","doi-asserted-by":"crossref","first-page":"464472","DOI":"10.1111\/j.1478-3231.1999.tb00078.x","article-title":"Enhanced expression of interleukin6 in chronic hepatitis C.","volume":"19","author":"Oyanagi","year":"1999","journal-title":"Liver"},{"key":"R6-13-20250207","doi-asserted-by":"crossref","first-page":"12201230","DOI":"10.1053\/j.gastro.2011.06.063","article-title":"Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection.","volume":"141","author":"Sandler","year":"2011","journal-title":"Gastroenterology"},{"key":"R7-13-20250207","doi-asserted-by":"crossref","first-page":"209218","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis.","volume":"115","author":"Bataller","year":"2005","journal-title":"J Clin Invest"},{"key":"R8-13-20250207","doi-asserted-by":"crossref","first-page":"15501558","DOI":"10.1038\/mt.2012.103","article-title":"Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the antiinflammatory potency of dexamethasone.","volume":"20","author":"Graversen","year":"2012","journal-title":"Mol Ther"},{"key":"R10-13-20250207","doi-asserted-by":"crossref","first-page":"347354","DOI":"10.1080\/07853890410033171","article-title":"CD163: a regulated hemoglobin scavenger receptor with a role in the antiinflammatory response.","volume":"36","author":"Moestrup","year":"2004","journal-title":"Ann Med"},{"key":"R11-13-20250207","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/j.1600-0609.2004.00318.x","article-title":"Soluble hemoglobinhaptoglobin scavenger receptor CD163 as a lineagespecific marker in the reactive hemophagocytic syndrome.","volume":"74","author":"Schaer","year":"2005","journal-title":"Eur J Haematol"},{"key":"R12-13-20250207","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1189\/jlb.1205756","article-title":"Pivotal advance: activation of cell surface Tolllike receptors causes shedding of the hemoglobin scavenger receptor CD163.","volume":"80","author":"Weaver","year":"2006","journal-title":"J Leukoc Biol"},{"key":"R13-13-20250207","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3109\/00365513.2011.626868","article-title":"Soluble CD163.","volume":"72","author":"Moller","year":"2012","journal-title":"Scand J Clin Lab Invest"},{"key":"R14-13-20250207","first-page":"13891393","article-title":"Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS.","volume":"60","author":"HollandFischer","year":"2011","journal-title":"Gut"},{"key":"R15-13-20250207","doi-asserted-by":"crossref","first-page":"173180","DOI":"10.1111\/j.1365-2036.2012.05134.x","article-title":"Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis.","volume":"36","author":"Gronbaek","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"key":"R16-13-20250207","doi-asserted-by":"crossref","first-page":"379384","DOI":"10.1016\/j.prp.2004.10.006","article-title":"Expression of CD163 in the liver of patients with viral hepatitis.","volume":"201","author":"Hiraoka","year":"2005","journal-title":"Pathol Res Pract"},{"key":"R17-13-20250207","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1007\/s00535-004-1493-8","article-title":"Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure.","volume":"40","author":"Hiraoka","year":"2005","journal-title":"J Gastroenterol"},{"key":"R18-13-20250207","doi-asserted-by":"crossref","first-page":"671676","DOI":"10.1016\/j.jhep.2007.05.014","article-title":"Soluble CD163 from activated macrophages predicts mortality in acute liver failure.","volume":"47","author":"Moller","year":"2007","journal-title":"J Hepatol"},{"key":"R19-13-20250207","doi-asserted-by":"crossref","first-page":"372374","DOI":"10.1016\/0168-8278(91)90084-O","article-title":"Classification of chronic viral hepatitis: a need for reassessment.","volume":"13","author":"Scheuer","year":"1991","journal-title":"J Hepatol"},{"key":"R20-13-20250207","doi-asserted-by":"crossref","first-page":"24672474","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.","volume":"94","author":"Brunt","year":"1999","journal-title":"Am J Gastroenterol"},{"key":"R21-13-20250207","doi-asserted-by":"crossref","first-page":"10861096","DOI":"10.1016\/0026-0495(79)90146-X","article-title":"Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations.","volume":"28","author":"Turner","year":"1979","journal-title":"Metabolism"},{"key":"R22-13-20250207","doi-asserted-by":"crossref","first-page":"9196","DOI":"10.1053\/gast.2003.50016","article-title":"Model for endstage liver disease (MELD) and allocation of donor livers.","volume":"124","author":"Wiesner","year":"2003","journal-title":"Gastroenterology"},{"key":"R23-13-20250207","doi-asserted-by":"crossref","first-page":"518526","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"key":"R24-13-20250207","doi-asserted-by":"crossref","first-page":"13171325","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIVHCV coinfection.","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"R25-13-20250207","doi-asserted-by":"crossref","first-page":"293299","DOI":"10.1080\/003655102760145852","article-title":"Characterization of an enzymelinked immunosorbent assay for soluble CD163.","volume":"62","author":"Moller","year":"2002","journal-title":"Scand J Clin Lab Invest"},{"key":"R26-13-20250207","doi-asserted-by":"crossref","first-page":"12931302","DOI":"10.1053\/j.gastro.2012.02.017","article-title":"Noninvasive methods to assess liver disease in patients with hepatitis B or C.","volume":"142","author":"Castera","year":"2012","journal-title":"Gastroenterology"},{"key":"R27-13-20250207","doi-asserted-by":"crossref","first-page":"378380","DOI":"10.1182\/blood.V99.1.378","article-title":"Identification of the hemoglobin scavenger receptorCD163 as a natural soluble protein in plasma.","volume":"99","author":"Moller","year":"2002","journal-title":"Blood"},{"key":"R28-13-20250207","doi-asserted-by":"crossref","first-page":"16271636","DOI":"10.1053\/j.gastro.2007.08.003","article-title":"Viral and host factors induce macrophage activation and loss of tolllike receptor tolerance in chronic HCV infection.","volume":"133","author":"Dolganiuc","year":"2007","journal-title":"Gastroenterology"},{"key":"R29-13-20250207","doi-asserted-by":"crossref","first-page":"27962802","DOI":"10.1128\/JVI.00996-08","article-title":"Macrophages in hepatitis B and hepatitis C virus infections.","volume":"83","author":"Heydtmann","year":"2009","journal-title":"J Virol"},{"key":"R30-13-20250207","doi-asserted-by":"crossref","first-page":"479487","DOI":"10.1189\/jlb.0207128","article-title":"Tolllike receptors 1 and 6 are involved in TLR2mediated macrophage activation by hepatitis C virus core and NS3 proteins.","volume":"82","author":"Chang","year":"2007","journal-title":"J Leukoc Biol"},{"key":"R31-13-20250207","doi-asserted-by":"crossref","first-page":"15131524","DOI":"10.1053\/j.gastro.2004.08.067","article-title":"Hepatitis C core and nonstructural 3 proteins trigger tolllike receptor 2mediated pathways and inflammatory activation.","volume":"127","author":"Dolganiuc","year":"2004","journal-title":"Gastroenterology"},{"key":"R32-13-20250207","doi-asserted-by":"crossref","first-page":"31653176","DOI":"10.4049\/jimmunol.175.5.3165","article-title":"Cytokine induction by the hepatitis B virus capsid in macrophages is facilitated by membrane heparan sulfate and involves TLR2.","volume":"175","author":"Cooper","year":"2005","journal-title":"J Immunol"},{"key":"R33-13-20250207","doi-asserted-by":"crossref","first-page":"e17484","DOI":"10.1371\/journal.pone.0017484","article-title":"Hyperactivated proinflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.","volume":"6","author":"Zhang","year":"2011","journal-title":"PLoS One"},{"key":"R34-13-20250207","doi-asserted-by":"crossref","first-page":"9951005","DOI":"10.2174\/1381612024606983","article-title":"Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection.","volume":"8","author":"Caradonna","year":"2002","journal-title":"Curr Pharm Des"},{"key":"R35-13-20250207","doi-asserted-by":"crossref","first-page":"380387","DOI":"10.1034\/j.1600-0676.2002.01666.x","article-title":"Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting.","volume":"22","author":"Kaser","year":"2002","journal-title":"Liver"},{"key":"R36-13-20250207","first-page":"153155","article-title":"Systemic endotoxemia during chronic viral hepatitis.","volume":"133","author":"Sozinov","year":"2002","journal-title":"Bull Exp Biol Med"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27129","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201408000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T16:48:00Z","timestamp":1738946880000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201408000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27129","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}