title: Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma.
abstract: BACKGROUND
  Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC.
  
  
  METHODS
  In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment.
  
  
  RESULTS
  In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5-8.0] mg/L) and CLD (6.1[3.6-9.6] mg/L) patients as compared to controls (2.0[1.5-2.7] mg/L, p < 0.001). sCD163 correlated with Child-Pugh and MELD scores in both HCC and CLD patients. Patients with high sCD163 levels had shorter progression-free survival (p < 0.001), but not overall survival (p = 0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts.
  
  
  CONCLUSIONS
  We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression.
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kazankov
authors.affiliation: b Department of Gastroenterology and Hepatology , Royal Melbourne Hospital , Melbourne , Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rode
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Kira
authors.initials: K
authors.lastname: Simonsen
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Gerda Elisabeth
authors.initials: GE
authors.lastname: Villadsen
authors.affiliation: b Department of Gastroenterology and Hepatology , Royal Melbourne Hospital , Melbourne , Australia.|c Department of Gastroenterology , Eastern Health , Melbourne , Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Nicoll
authors.affiliation: d Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: e Victorian Liver Transplant Unit and Department of Gastroenterology , Austin Hospital , Melbourne , Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lim
authors.affiliation: e Victorian Liver Transplant Unit and Department of Gastroenterology , Austin Hospital , Melbourne , Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
authors.affiliation: f Department of Gastroenterology , Western Hospital , Melbourne , Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Kronborg
authors.affiliation: f Department of Gastroenterology , Western Hospital , Melbourne , Australia.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Arachchi
authors.affiliation: g Epicentre , Royal Melbourne Hospital , Melbourne , Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gorelik
authors.affiliation: g Epicentre , Royal Melbourne Hospital , Melbourne , Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: h Medical Research Laboratory, Department of Clinical Medicine, Health, Aarhus University , Aarhus , Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001315:Australia; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016022:Case-Control Studies; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000473:pathology; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
keywords: Biomarker; immunity; inflammation; liver disease; prediction; tumor associated macrophages