Introduction 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 (r2=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.
Conclusion 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.
- Kupffer cells
- portal venous pressure gradient
- bacterial translocation
- liver cirrhosis
- portal hypertension
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Funding This study was supported by grants from the Beckett Foundation; Clinical Institute, Aarhus University; the Danish Agency for Science, Technology and Innovation; the Lundbeck Foundation; the NOVO Nordic Foundation; and the A.P. Møller Foundation for the Advancement of Medical Science.
Competing interests None.
Ethics approval This study was conducted with the approval of the Central Denmark Region Committees on Biomedical Research Ethics and by the ethics committee and research committee of the University of Rome “La Sapienza”.
Provenance and peer review Not commissioned; externally peer reviewed.