Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 26, 2021; 9(6): 1386-1393
Published online Feb 26, 2021. doi: 10.12998/wjcc.v9.i6.1386
Wilson disease — the impact of hyperimmunity on disease activity: A case report
Wolfgang Stremmel, Thomas Longerich, René Liere, Vladimir Vacata, Josef van Helden, Ralf Weiskirchen
Wolfgang Stremmel, Pracice for Gastroenterology, Medical Center Baden-Baden, Baden-Baden D-76530, Germany
Thomas Longerich, Department of General Pathology, University Heidelberg Hospital, Institute of Pathology, University of Heidelberg, Heidelberg D-69115, Germany
René Liere, Vladimir Vacata, Josef van Helden, MVZ Dr. Stein + Kollegen, Labor Mönchengladbach, Mönchengladbach D-41069, Germany
Ralf Weiskirchen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, Rheinisch-Westfaelische Technische Hochschule University Hospital Aachen, Aachen D-52074, Germany
Author contributions: Stremmel W contributed the conceptualization; Stremmel W, Longerich T, Liere R, Vacata V, van Helden J and Weiskirchen R contributed validation; Stremmel W and Weiskirchen R wrote original draft preparation; Stremmel W, Longerich T and Weiskirchen R wrote review and editing; Liere R and Vacata V contributed the software.
Informed consent statement: Informed consent was given from the patient and her family.
Conflict-of-interest statement: The authors have nothing to declare.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Wolfgang Stremmel, MD, Senior Scientist, Pracice for Gastroenterology, Medical Center Baden-Baden, Im Neuenheimer Feld 410, Baden-Baden D-76530, Germany.
Received: September 24, 2020
Peer-review started: September 24, 2020
First decision: December 4, 2020
Revised: December 8, 2020
Accepted: December 23, 2020
Article in press: December 23, 2020
Published online: February 26, 2021

In Wilson disease lack of biliary copper excretion causes hepatocellular injury by accumulation of free toxic copper. Its overspill to serum accounts for neuronal damage as second common manifestation. Therapy with copper chelators or zinc targets the removal of this free copper. However, in some patients liver disease persists for unknown reason despite normalized free copper. The discovery of a hyperimmunity as a contributing pathogenetic factor was discovered in this case report with implication also for other liver diseases.


A 9-year-old girl was diagnosed in August 2009 by family screening of having asymptomatic Wilson disease with elevated transaminases. Already at time of diagnosis antinuclear antibodies (ANA) were elevated without hyperimmunoglobulinemia (immunoglobulin G, IgG). After one year of therapy with D-penicillamine transaminases normalized together with free serum copper. Under continuous therapy with copper chelators free copper remained normal until today, whereas transaminases raised to alanine aminotransferase values of 571 U/L in December 2019. For hyperimmunity a tentative steroid course on top of D-penicillamine improved transaminases. Thus, hyperimmunity may have impact on liver inflammation after control of the metabolic disturbance. A retrospective cohort study confirmed the common association of elevated transaminases with ANA, but no IgG elevation.


This hyperimmune-triggered condition may represent a new entity which per se or on top of other liver diseases induces liver inflammation responsive to steroids.

Keywords: Wilson disease, Copper metabolism, Antinuclear antibodies, Diagnosis, Steroid therapy, Case report

Core Tip: Variable courses of metabolic liver diseases remain obscure. A 9-year-old girl with Wilson disease had concomitant antinuclear antibodies elevation without immunoglobulin G elevation. Already after one year of therapy with copper chelators the free copper as treatment target was normalized as well as transaminases. Six years later transaminases (alanine aminotransferase) rose despite normalized free copper up to 571 U/L in December 2019. A short-term steroid therapy, improved transaminases significantly. As underlying course, such a neglected hyperimmune state without immunoglobulin elevation was verified in a cohort of 5.789 liver disease patients and may represent a new entity explaining liver disease activation.