title: Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS.
abstract: BACKGROUND
  Hepatic macrophages (Kupffer cells) undergo inflammatory activation during the development of portal hypertension in experimental cirrhosis; this activation may play a pathogenic role or be an epiphenomenon. Our objective was to study serum soluble CD163 (sCD163), a sensitive marker of macrophage activation, before and after reduction of portal venous pressure gradient by insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis.
  
  
  METHODS
  sCD163 was measured in 11 controls and 36 patients before and 1, 4 and 26 weeks after TIPS. We used lipopolysaccharide binding protein (LBP) levels as a marker of endotoxinaemia. Liver function and clinical status of the patients were assessed by galactose elimination capacity and Model for End Stage Liver Disease score.
  
  
  RESULTS
  The sCD163 concentration was more than threefold higher in the patients than in the controls (median 5.22 mg/l vs 1.45 mg/l, p<0.001). The sCD163 was linearly related to the portal venous pressure gradient (r(2)=0.24, p<0.001), also after adjustment for cirrhosis status. The sCD163 concentration was 12% higher in the hepatic than in the portal vein (p<0.02). The LBP level was 70% higher in the patients (52.2 vs 30.4 μg/l, p<0.001). During follow-up after TIPS, the sCD163 concentration did not change while LBP almost normalised.
  
  
  CONCLUSIONS
  Kupffer cells were activated in patients with liver cirrhosis in parallel with their portal hypertension. The activation was not alleviated by the mechanical reduction of portal hypertension and the decreasing signs of endotoxinaemia. The findings suggest that Kupffer cell activation is a constitutive event that may play a pathogenic role for portal hypertension.
authors.affiliation: Department of Medicine V (Hepato and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark. phf@svf.au.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Holland-Fischer
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
authors.forename: Thomas Damgaard
authors.initials: TD
authors.lastname: Sandahl
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Oliviero
authors.initials: O
authors.lastname: Riggio
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ridola
authors.forename: Niels Kristian
authors.initials: NK
authors.lastname: Aagaard
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D007111:Immunity, Cellular; D007728:Kupffer Cells / Q000276:immunology*; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology* / Q000601:surgery; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000276:immunology; D017082:Portal Pressure / Q000502:physiology*; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011379:Prognosis; D020127:Recovery of Function / Q000502:physiology*; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30