High hepatic macrophage activation and low liver function in stable Wilson patients - a Danish cross-sectional study

Jessica BjörklundEmail author View ORCID ID profile,
Tea Lund Laursen,
Thomas Damgaard Sandahl,
Holger Jon Møller,
Hendrik Vilstrup,
Peter Ott and
Henning Grønbæk

Orphanet Journal of Rare Diseases201813:169

https://doi.org/10.1186/s13023-018-0910-7

Received: 6 June 2018
Accepted: 12 September 2018
Published: 21 September 2018

Abstract

Background

Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson’s disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of soluble (s)CD163, metabolic liver function by the galactose elimination capacity (GEC), and fibrosis by Fibroscan. We investigated the associations between sCD163, selected inflammatory cytokines, GEC, and liver fibrosis in Danish WD patients.

Methods

In a cross-sectional design, we studied 29 stable and well-treated patients (male/female15/14) with a median age of 35 years (IQR 24–50). P-sCD163 and cytokines were measured by ELISA. The GEC was measured by intra-venous galactose loading.

Results

The median P-sCD163 value at 2.96 mg/L (1.97–3.93) was high in the normal range (0.7–3.9) and seven patients (24%) had a value above the upper normal value. sCD163 correlated with TNF-α, IL-6 and IL-8 (rho> 0.50, p < 0.005). A higher sCD163 value was closely associated with a lower GEC (rho = − 0.51, p = 0.02). sCD163 was not related to the liver fibrosis indices.

Conclusions

Stable WD patients showed various degrees of Kupffer cell activation which was accompanied by loss of metabolic liver function. Neither activation nor liver function was related to liver fibrosis. The findings suggest that in WD inflammatory Kupffer cell activation may be involved in the loss of liver function over time. sCD163 may serve as a non-invasive biomarker of loss of liver function in WD, which the degree of fibrosis evidently may not.

This study is registered at clinical trials with name: “sCD163 and sMR in Wilsons Disease - Associations With Disease Severity and Fibrosis”, NCT02702765. Date of registration: 26.02.16. Date of enrolment of the first participant to the trial: 17.03.16. ULR: https://clinicaltrials.gov/ct2/show/NCT02702765.