Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis

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. Aim 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 (ChildPugh CP-A: n similar to=similar to 26, CP-B: n similar to=similar to 29, CP-C: n similar to=similar to 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by ChildPugh and MELD-score. Results In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 similar to+/-similar to 2.5 vs. 1.6 similar to+/-similar to 0.5 similar to mg/L, P similar to<similar to 0.001). sCD163 was also higher, as measured in steps by CP-score (P similar to<similar to 0.001). The HVPG rose steeply to an asymptote of 22 similar to mmHg with sCD163 up to about 5 similar to 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 similar to>similar to 3.95 similar to mg/L (upper normal limit) predicted HVPG similar to=similar to 10 similar to mmHg with a positive predictive value of 0.99. Conclusions Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing ChildPugh 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.