title: Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis.
abstract: BACKGROUND
  Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells.
  
  
  OBJECTIVE
  To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis.
  
  
  METHODS
  We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score.
  
  
  RESULTS
  In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99.
  
  
  CONCLUSIONS
  Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention.
authors.affiliation: Department of Medicine V, Aarhus University Hospital, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Grønbaek
authors.forename: T D
authors.initials: TD
authors.lastname: Sandahl
authors.forename: C
authors.initials: C
authors.lastname: Mortensen
authors.forename: H
authors.initials: H
authors.lastname: Vilstrup
authors.forename: H J
authors.initials: HJ
authors.lastname: Møller
authors.forename: S
authors.initials: S
authors.lastname: Møller
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002302:Cardiac Output / Q000502:physiology; D016022:Case-Control Studies; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood* / Q000209:etiology; D007728:Kupffer Cells / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008262:Macrophage Activation; D008875:Middle Aged; D015999:Multivariate Analysis; D017082:Portal Pressure / Q000502:physiology; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000097:blood*; D012720:Severity of Illness Index; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface