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The macrophage activation marker soluble CD163 is elevated and associated with liver disease phenotype in patients with Wilson’s disease

Posted on 2020-07-03 - 04:36
Abstract Background Macrophages play a significant role in liver disease development and progression. The macrophage activation marker soluble (s)CD163 is associated with severity and prognosis in a number of different acute and chronic liver diseases but has been only sparsely examined in Wilson’s disease (WD). We investigated sCD163 levels in patients with acute and chronic WD and hypothesized associations with liver disease phenotype and biochemical markers of liver injury. Methods We investigated sCD163 in two independent cohorts of WD patients: 28 patients with fulminant WD from the US Acute Liver Failure (ALF) Study Group registry and 147 patients with chronic disease from a German WD registry. We included a control group of 19 healthy individuals. Serum sCD163 levels were measured by ELISA. Liver CD163 expression was determined by immunohistochemistry. Results In the ALF cohort, median sCD163 was 10-fold higher than in healthy controls (14.6(2.5–30.9) vs. 1.5(1.0–2.7) mg/L, p < 0.001). In the chronic cohort, median sCD163 was 2.6(0.9–24.9) mg/L. There was no difference in sCD163 according to subgroups based on initial clinical presentation, i.e. asymptomatic, neurologic, hepatic, or mixed. Patients with cirrhosis at the time of diagnosis had higher sCD163 compared with those without cirrhosis (3.0(1.2–24.9) vs. 2.3(0.9–8.0) mg/L, p < 0.001); and both cohorts significantly lower than the ALF patients. Further, sCD163 correlated positively with ALT, AST, GGT and INR (rho = 0.27–0.53); and negatively with albumin (rho = − 0.37), (p ≤ 0.001, all). We observed immunohistochemical CD163 expression in liver tissue from ALF patients. Conclusions Although sCD163 is not specific for WD, it was elevated in WD patients, especially in those with ALF. Further, sCD163 was higher in patients with cirrhosis compared to patients without cirrhosis and associated with biochemical markers of liver injury and hepatocellular function. Thus, macrophage activation is evident in WD and associates with liver disease phenotype and biochemical parameters of liver disease. Our findings suggest that sCD163 may be used as a marker of liver disease severity in WD patients.

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Orphanet Journal of Rare Diseases

AUTHORS (14)

Emilie Glavind
Daniel N. Gotthardt
Jan Pfeiffenberger
Thomas Damgaard Sandahl
Teodora Bashlekova
Gro Linno Willemoe
Jane Preuss Hasselby
Karl Heinz Weiss
Holger Jon Møller
Hendrik Vilstrup
William M. Lee
Michael L. Schilsky
Peter Ott
Henning Grønbæk
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