sCD163 and sMR in Wilsons Disease - Associations With Disease Severity and Fibrosis

Study Overview
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Brief Summary
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The aim is to investigate macrophage activation markers and correlations to liver fibrosis in patients with Wilsons Disease. Researchers wish to investigate associations to neurologic and metabolic liver function. Researchers will assess this by comparing blood samples with fibrosis and liver function analyses. This study provides new insight into macrophages and their involvement in Wilsons Disease.

Official Title
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Macrophages and the Macrophage Activation Markers sCD163 and Mannose Receptor (sMR) in Patients With Wilsons Disease - Associations With Liver Disease Severity and Fibrosis

Conditions
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Wilsons Disease

Intervention / Treatment
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* Procedure: Fibroscan
* Procedure: Ultrasound
* Drug: Galactose
* Procedure: Liver biopsy
* Procedure: Functional hepatic nitrogen clearance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with Wilsons disease Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wilsons disease<br>All patients will receive all interventions (galactose elimination capacity test , ultrasound, fibroscan, continuous reaction time test and functional hepatic nitrogen clearance ), except liver biopsy. | Procedure: Fibroscan<br>* Liver fibrosis will be determined using fibroscan, and reported as changes in the amount of fibrosis in the liver. The fibroscan is a non-invasive procedure<br>Procedure: Ultrasound<br>* Ultrasound is a non-invasive procedure<br>Drug: Galactose<br>* Galactose elimination capacity is performed to evaluate metabolic liver function. The metabolic liver function test galactose elimination capacity requires a 6-hour fast, the infusion of galactose, blood sampling from the ear lobe, and collection of urine for 4 hours.<br>* Other names: Galactose elimination capacity;Procedure: Liver biopsy<br>* Histological disease activity at time of diagnosis evaluating if any liver fibrosis<br>Procedure: Functional hepatic nitrogen clearance<br>* Functional hepatic nitrogen clearance to evaluate metabolic liver function Functional hepatic nitrogen clearance requires a 12-hour fast, two venflons, the infusion of alanine, and urine sampling for 4 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the macrophage activation markers sCD163 | For the investigations a total of 100 ml of blood is drawn, all stored in a research biobank. | Baseline, 1 year, 2 year, 3 year | 
| Measurement of soluble mannose receptor (sMR) | For the investigations a total of 100 ml of blood is drawn, all stored in a research biobank. | Baseline, 1 year, 2 year, 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary copper excretion in 24 hour urine collection | The patient collects urine for 24 hours at home in a designated container, which is handed out at the department. The container is kept refrigerated and is brought to the control | Baseline, 1 year, 2 year, 3 year | 
| Ultrasound is performed for signs of liver cirrhosis. | Ultrasound is a non-invasive procedure. Signs og liver cirrhosis by ultrasound are surface modularity, a smaller liver, heterogeneous echo texture and signs of portal hypertension. | Baseline, 1 year, 2 year, 3 year | 
| Fibroscan is performed to evaluate liver stiffness (fibrosis) | Liver fibrosis will be determined using fibroscan, and reported as changes in the amount of fibrosis in the liver. The fibroscan is a non-invasive procedure. | Baseline, 1 year, 2 year, 3 year | 
| Continous Reaction Time to evaluate brain dysfunction | Continous Reaction Time is a computerized 10 minutes test that measures and combines motor reaction speed and sustained attention. | Baseline, 1 year, 2 year, 3 year | 
| Galactose elimination capacity is performed to evaluate metabolic liver function | The metabolic liver function test Galactose elimination capacity requires a 6-hour fast, the infusion of galactose, blood sampling from the ear lobe, and collection of urine for 4 hours. | Baseline, 1 year, 2 year, 3 year | 
| Histological disease activity at time of diagnosis and liver biopsy, evaluating if any liver fibrosis | Liver fibrosis will be also be determined on liver biopsies. | Baseline, 1 year, 2 year, 3 year | 
| Functional hepatic nitrogen clearance to evaluate metabolic liver function | Functional hepatic nitrogen clearancerequires a 12-hour fast, two venflons, the infusion of alanine, and urine sampling for 4 hours. It evaluates the metabolic liver function by measuring the clearance of alanine from blod by analyzing the amount og urea in the urine collected 4 hours after the start og the alanine infusion. | Baseline, 1 year, 2 year, 3 year | 
| The Portosystemic Encephalopathy to evaluate brain dysfunction | The Portosystemic Encephalopathy test is a 15-minute paper-pencil test battery comprised of 5 sub-tests: Digit Symbol test (DST), Number Connection Test A (NCT-A), Number Connection Test B (NCT-B), Serial Dotting Test (SDOT), and Line Tracing Test (LTT, time and errors). | Baseline, 1 year, 2 year, 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sCD163, liver cirrhosis, disease severity