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

Summary Background Activation of K upffer 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) CD 163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis. Methods We measured sCD 163 concentration and the hepatic venous pressure gradient ( HVPG ) by liver vein catheterisation in 81 cirrhosis patients ( C hild– P ugh 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 C hild– P ugh and MELD ‐score. Results In cirrhosis, sCD 163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD 163 was also higher, as measured in steps by CP ‐score ( P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD 163 up to about 5 mg/L and not to higher values with higher sCD 163. In a multivariate analysis, sCD 163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD 163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99. Conclusions Circulating sCD 163 originating from activated K upffer cells is increased in cirrhosis with increasing C hild– P ugh 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.