title: Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C.
abstract: 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, P < 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kazankov
authors.forename: Francisco
authors.initials: F
authors.lastname: Barrera
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016015:Logistic Models; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012307:Risk Factors; D012995:Solubility; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface