• Chelation
• Copper overload
• NBMI
• Toxic milk mouse
• Wilson's disease

• Animals
• Hepatolenticular Degeneration/drug therapy
• Hepatolenticular Degeneration/pathology
• Hepatolenticular Degeneration/metabolism
• Hepatolenticular Degeneration/genetics
• Humans
• Copper-Transporting ATPases/genetics
• Mice
• Chelating Agents/pharmacology
• Copper/metabolism
• Hep G2 Cells
• Liver/metabolism
• Liver/drug effects
• Liver/pathology
• Disease Models, Animal
• Phthalic Acids/pharmacology
• Copper Sulfate/toxicity
• Cation Transport Proteins/genetics
• Adenosine Triphosphatases/genetics
• Male

• acute hepatitis
• acute liver failure
• ceruloplasmin
• copper
• liver transplantation

• Cancer
• Cancer therapies
• Copper
• Copper homeostasis
• Nanomaterials

• Humans
• Copper/metabolism
• Copper/therapeutic use
• Neoplasms/drug therapy
• Carcinogenesis

• 2022AH050779 Anhui Provincial University Research Projects
• 202004j07020036 Key Research and Development Project of Anhui Provincial Department of Science and Technology
• 2020xsxxkc247 Key Teaching Research Project of Anhui Provincial Department of Education
• 320.6750.19092-19 Wu Jieping Medical Foundation

• hepatolenticular degeneration
• hypersplenism
• liver function
• splenectomy

• Child
• Humans
• Hepatolenticular Degeneration/complications
• Hypersplenism/etiology
• Hypersplenism/surgery
• Retrospective Studies
• Splenectomy/methods
• Treatment Outcome
• Follow-Up Studies
• Liver Cirrhosis/surgery

• Gene therapy
• Genetics
• Hepatology
• Monogenic diseases

• Mice
• Animals
• Hepatolenticular Degeneration/therapy
• Hepatolenticular Degeneration/drug therapy
• Copper/metabolism
• Gene Editing
• Hepatocytes/metabolism

• Fondazione Telethon

• Classification
• Combined
• Dystonia
• Genetics
• Isolated

• Humans
• Dystonia
• Syndrome
• Dystonic Disorders/genetics
• Cerebellum
• Dopamine

• Hepatolenticular degeneration
• congenital abnormalities
• pregnancy
• zinc

Both hepatolenticular degeneration (HLD) and viral hepatitis B (HBV) can cause hypersplenism, but whether splenectomy is needed or can be performed in HLD patients associated with hypersplenism is still controversial. At present, HLD combined with hypersplenism has not been listed as the indication of splenectomy.

This study aimed to investigate the efficacy, risks, and postoperative complications of splenectomy in HLD patients associated with hypersplenism.

We retrospectively analyzed the clinical data of 180 HLD patients with hypersplenism who underwent splenectomy in the Department of General Surgery, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, from January 2001 to December 2015. To evaluate the efficacy of splenectomy, the hemogram of white blood cells (WBC), red blood cells (RBC), platelets (PLT), and the liver function indexes including alanine aminotransferase, aspartate aminotransferase, and total bilirubin were recorded before surgery and 1, 3, 5, 7, and 14 days after surgery. In addition, the clinical data of 142 HBV patients with hypersplenism who underwent splenectomy over the same period were also recorded and compared with that of HLD patients. In particular, aiming to assess the risks of splenectomy in HLD, we also compared postoperative complications and 36-month mortality between the two groups.

The level of WBC, RBC, and PLT were all elevated after splenectomy in both the HLD group and the HBV group. However, there was no significant difference in the variation of hemogram after splenectomy between the two groups (P > 0.05). Similarly, the variation of liver function indexes showed no statistical difference between the two groups. In terms of the incidence of postoperative complications including abdominal bleeding, pancreatic leakage, portal vein thrombosis treatment, incision infection, lung infection, and 36-month mortality, there were no significant differences between the two groups.

After splenectomy, the hemogram as well as liver function in the HLD group improved a lot and showed a consistent tendency with that in the HBV group. Meanwhile, compared to the HBV group, there was no significant difference in the incidence of postoperative complications in the HLD group. All these results indicate that splenectomy in HLD patients combined with hypersplenism is completely feasible and effective.

• National Key Clinical Specialty Construction Project of the Twelfth Five-Year Plan

Wilson disease (WD) is a genetic disorder of copper homeostasis, caused by deficiency of the copper transporter ATP7B. Gene therapy with recombinant adeno-associated vectors (AAV) holds promises for WD treatment. However, the full-length human ATP7B gene exceeds the limited AAV cargo capacity, hampering the applicability of AAV in this disease context. To overcome this limitation, we designed a dual AAV vector approach using split intein technology. Split inteins catalyze seamless ligation of two separate polypeptides in a highly specific manner. We selected a DnaE intein from Nostoc punctiforme (Npu) that recognizes a specific tripeptide in the human ATP7B coding sequence. We generated two AAVs expressing either the 5′-half of a codon-optimized human ATP7B cDNA followed by the N-terminal Npu DnaE intein or the C-terminal Npu DnaE intein followed by the 3′-half of ATP7B cDNA, under the control of a liver-specific promoter. Intravenous co-injection of the two vectors in wild-type and Atp7b^−/− mice resulted in efficient reconstitution of full-length ATP7B protein in the liver. Moreover, Atp7b^−/− mice treated with intein-ATP7B vectors were protected from liver damage and showed improvements in copper homeostasis. Taken together, these data demonstrate the efficacy of split intein technology to drive the reconstitution of full-length human ATP7B and to rescue copper-mediated liver damage in Atp7b^−/− mice, paving the way to the development of a new gene therapy approach for WD.

• ATP7B
• Wilson disease
• ceruloplasmin
• copper metabolism
• genotype-phenotype correlation
• polarized trafficking

Metal elements are present in the human body, and their levels in the blood have important impacts on health. In this study, 2488 Chinese individuals were included in a genome-wide association study of 21 serum metal levels, with approximately 179,000 East Asian individuals in a bidirectional two-sample Mendelian randomization (MR) analysis, and 628,000 Europeans in a two-sample MR analysis. We identified two single nucleotide polymorphisms (SNPs) rs35691438 and rs671 that were significantly associated with serum copper levels (SCLs). The bidirectional two-sample MR analysis in the East Asian population showed that gamma-glutamyl transpeptidase levels have a causal effect on SCLs. SCLs have causal effects on six outcomes, namely risks of esophageal varix, glaucoma, sleep apnea syndrome, and systemic lupus erythematosus, white blood cell count, and usage of drugs affecting bone structure and mineralization. The two-sample MR analyses in the European population showed causal effects of erythrocyte copper levels on risks of carpal tunnel syndrome and compression fracture. Our results provide original insights into the causal relationship between blood metal levels and multiple human phenotypes.

A genome-wide association study in a Chinese population identifies SNPs associated with serum copper levels. Mendelian randomization analysis reveals causal effects on multiple human phenotypes in East Asian and European populations.

Dystonia is a hyperkinetic movement disorder characterized by abnormal movement or posture caused by excessive muscle contraction. Because of its wide clinical spectrum, dystonia is often underdiagnosed or misdiagnosed. In clinical practice, dystonia could often present in association with other movement disorders. An accurate physical examination is essential to describe the correct phenomenology. To help clinicians reaching the proper diagnosis, several classifications of dystonia have been proposed. The current classification consists of axis I, clinical characteristics, and axis II, etiology. Through the application of this classification system, movement disorder specialists could attempt to correctly characterize dystonia and guide patients to the most effective treatment. The aim of this article is to describe the phenomenological spectrum of dystonia, the last approved dystonia classification, and new emerging knowledge.

Wilson’s disease (WD), a rare genetic disorder characterized by copper accumulation, leads to a spectrum of hepatic dysfunction including liver cirrhosis, fulminant liver failure, and chronic hepatitis. Its manifestations could involve musculoskeletal, hematologic, neuropsychiatric, or renal systems. We present the case of a 27-year-old female with a past medical history of alcohol use disorder who presented with acute confusion, worsening abdominal distension, bilateral lower limb edema, and jaundice.The initial presentation was concerning for acute alcoholic hepatitis and decompensated alcoholic cirrhosis attributed to ongoing heavy alcohol consumption. However, due to the patient’s young age, the severity of presentation, and the pattern of liver enzyme elevation, further workup was conducted to rule out concurrent pathologies. Viral, autoimmune, and metabolic workups were unrevealing. Subsequently, low ceruloplasmin levels and elevated urinary copper levels led to a diagnosis of WD with concomitant alcoholic liver disease.

The coexistence of WD and alcohol-associated liver disease (ALD) has not been well described in the literature. Laboratory testing including alkaline phosphatase (ALP), bilirubin, and serum aminotransferases provides the most rapid and accurate method for diagnosing ALD due to WD, given that the conventional screening tests such as ceruloplasmin are less sensitive and specific in identifying patients with acute liver disease secondary to WD.

• alcoholic liver disease
• case report
• ceruloplasmin
• liver cirrhosis
• wilson’s disease

• ATP7B gene
• Leipzig scale
• Wilson-like
• Wilson’s disease
• biomarkers
• genetic modifiers

• PI18/00147 Instituto de Salud Carlos III
• PI19/01360 Instituto de Salud Carlos III
• PROMETEO/2018/135 Generalitat Valenciana
• FPAA-Wilson Fundació Per Amor a l'Art (FPAA)
• Unit CB06/04/0065 CIBERhed Instituto de Salud Carlos III

The association of movement disorders with structural or functional hepatic disease occurs in three principal scenarios: (1) combined involvement of both organ systems from a single disease entity, (2) nervous system dysfunction resulting from exposure to toxic compounds in the setting of defective hepatic clearance, or (3) hepatic and/or neurological injury secondary to exposure to exogenous drugs or toxins. An important early step in the workup of any patient with combined movement disorders and liver disease is the exclusion of Wilson's disease. Diagnostic delay remains common for this treatable disorder, and this has major implications for patient outcomes. Thereafter, a structured approach integrating variables such as age of onset, tempo of progression, nature and severity of liver involvement, movement disorder phenomenology, exposure to drugs/toxins and laboratory/neuroimaging findings is key to ensuring timely diagnosis and disease‐specific therapy. Herein, we provide an overview of disorders which may manifest with a combination of movement disorders and liver disease, structured under the three headings as detailed above. In each section, the most common disorders are discussed, along with important clinical pearls, suggested diagnostic workup, differential diagnoses and where appropriate, treatment considerations.

• liver diseases
• movement disorders

Wilson disease is an autosomal recessive condition manifested when abnormal copper accumulation in the body particularly involving many organs such as brain, liver, and cornea. Diagnosis is challenging with the completion of tests in blood and urine, a liver biopsy, and clinical evaluation. ATP7B mutations with more than 600 identified variants are the genetic disorders of Wilson disease.

We report an adolescent case with no family history presented with extrapyramidal dyskinesia. Other symptoms include liver cirrhosis and Kayser–Fleischer ring. The typical presentation of blood test results and brain MRI images helps us to suspect Wilson disease in this case. We confirmed to have a p.R778L form and a p.S105X form in ATP7B mutations. After combining therapy with trihexyphenidyl and trientine, the patient’s medical condition was stable and no side effects were observed.

Screening for the diagnosis of Wilson disease is essential in helping patients benefit from early treatment and genetic counseling.

• ATP7B
• Movement disorders
• Wilson disease
• p.R778L
• p.S105X

Apathy is one of the neuropsychiatric symptoms of Wilson’s disease (WD) which typically affects the brain’s fronto-basal circuits. Lack of agreed diagnostic criteria and common use of self-description assessment tools lead to underestimation of this clinical phenomenon. The aim of this study was to investigate whether subjective and informant-based clinical features of apathy in patients with WD enable clinicians to make a valid diagnosis.

Multiple aspects of goal-oriented behavior were assessed in 30 patients with the neurological form of WD and 30 age-matched healthy participants using two questionnaires, the Lille Apathy Rating Scale (LARS) and the Dysexecutive Questionnaire (DEX). Both included a self-descriptive and a caregiver/proxy version. Cognitive functioning was estimated with the use of Addenbrooke’s Cognitive Examination-Revised.

Patients obtained significantly worse scores on all clinical scales when more objective measures were considered. Features of apathy and executive dysfunction were revealed in patients’ caregiver versions of LARS and DEX, which may indicate poor self-awareness of patients with WD. Roughly 30% of participants were likely to present with clinically meaningful symptoms, independent of cognitive dysfunction.

Methods relying on self-description appear inferior to informant-based scales when diagnosing apathy. More objective criteria and measurement tools are needed to better understand this clinical syndrome.

• Apathy syndrome
• Cognitive impairment
• Psychopathology
• Self-description
• Wilson’s disease

The clinical data of safety and efficacy of a combined treatment with dimercaptosuccinic acid (DMSA) and Zinc with 2 years’ follow-up in 60 neurological Wilson’s disease (WD) patients was retrospectively analyzed. All the patients included in the present study were newly diagnosed and initialized with D-penicillamine (DPA) treatment but were found to have either neurological deterioration or allergy, and their treatment was switched to a combined treatment of DMSA and Zinc. Fifty-one patients (85%) had the neurological symptoms improved 1 and 2 years after treatment, 7 (11.67%) experienced a stable neurological condition, and 2 (3.33%) suffered deterioration of neurological symptoms. No early neurological deterioration was observed in all patients. Twenty-five percent patients experienced mild adverse reactions which did not require a discontinuation of the DMSA and Zinc treatment. Our study confirmed the safety and efficacy of the combined DMSA and Zinc therapy as an initial and probably long-term treatment in neurological WD patients.

• Allergy
• D-penicillamine
• Dimercaptosuccinic acid
• Neurological deterioration
• Wilson's disease
• Zinc

Essential metals such as copper (Cu) and zinc (Zn) are important cofactors in diverse cellular processes, while metal imbalance may impact or be altered by disease state. Cu is essential for aerobic life with significant functions in oxidation-reduction catalysis. This redox reactivity requires precise intracellular handling and molecular-to-organismal levels of homeostatic control. As the central organ of Cu homeostasis in vertebrates, the liver has long been associated with Cu storage disorders including Wilson Disease (WD) (heritable human Cu toxicosis), Idiopathic Copper Toxicosis and Endemic Tyrolean Infantile Cirrhosis. Cu imbalance is also associated with chronic liver diseases that arise from hepatitis viral infection or other liver injury. The labile redox characteristic of Cu is often discussed as a primary mechanism of Cu toxicity. However, work emerging largely from the study of WD models suggests that Cu toxicity may have specific biochemical consequences that are not directly attributable to redox activity. This work reviews Cu toxicity with a focus on the liver and proposes that Cu accumulation specifically impacts Zn-dependent processes. The prospect that Cu toxicity has specific biochemical impacts that are not entirely attributable to redox may promote further inquiry into Cu toxicity in WD and other Cu-associated disorders.

• Wilson Disease
• copper
• copper toxicity
• oxidative stress
• zinc

• Achilles contracture
• Lambrinudi arthrodesis
• Wilson’s disease
• equinocavovarus deformity

A plethora of heterogeneous movement disorders is grouped under the umbrella term dystonia. The clinical presentation ranges from isolated dystonia to multi-systemic disorders where dystonia is only a co-occurring sign. In the past, definitions, nomenclature, and classifications have been repeatedly refined, adapted, and extended to reflect novel findings and increasing knowledge about the clinical, etiologic, and scientific background of dystonia. Currently, dystonia is suggested to be classified according to two axes. The first axis offers precise categories for the clinical presentation grouped into age at onset, body distribution, temporal pattern and associated features. The second, etiologic, axis discriminates pathological findings, as well as inheritance patterns, mode of acquisition, or unknown causality. Furthermore, the recent recommendations regarding terminology and nomenclature of inherited forms of dystonia and related syndromes are illustrated in this article. Harmonized, specific, and internationally widely used classifications provide the basis for future systematic dystonia research, as well as for more personalized patient counseling and treatment approaches.

• Clinical classification
• Disease etiology
• Dystonia
• Nomenclature

• Age of Onset
• Causality
• Dystonia/diagnosis
• Dystonia/etiology
• Dystonic Disorders/diagnosis
• Dystonic Disorders/etiology
• Humans
• Movement Disorders

• Deutsche Forschungsgemeinschaft
• Dystonia Medical Research Foundation
• Projekt DEAL

• Artificial intelligence
• Deep learning
• Diagnostic ratio
• Machine learning
• Performance
• Reliability
• Stability
• Three-dimensional optimization
• Transfer learning
• Wilson’s disease

(1) Background: Wilson’s disease (WD) is an inherited autosomal recessive disorder with the excessive deposition of copper into different organs, including the heart. Previous studies showed structural cardiac changes even in patients with no signs of heart failure. The aim of this study was to perform cardiac magnetic resonance-based strain analysis in WD patients, as it is a powerful independent predictor of mortality. (2) Methods: We conducted a prospective cardiac magnetic resonance study that included 61 patients and 61 age and sex-matched controls, and performed strain analysis of the left and right ventricle. (3) Results: Left ventricular global longitudinal strain (GLS) as a prognostic marker of increased mortality was not altered (control −22.8 (4.8) % vs. WD patients −21.8 (5.1) %, p = 0.124). However, 4 of the 61 patients had a markedly reduced GLS. Global circumferential strain did not significantly differ between the groups either (p = 0.534). WD patients had significantly reduced global radial strain (p = 0.002). Right ventricular GLS was also significantly reduced in WD patients (p = 0.01). (4) Conclusions: Strain analysis revealed functional impairment of the left and right ventricle in a small number of patients as a potential early sign of cardiac manifestation in asymptomatic WD patients.

• Wilson’s disease
• cardiac magnetic resonance imaging
• feature-tracking
• global longitudinal strain
• strain analysis

• Ceruloplasmin
• Genetics
• Wilson disease

• copper
• iron
• microelements
• pregnancy
• zinc

• Copper/metabolism
• Embryonic Development
• Female
• Humans
• Iron/metabolism
• Pregnancy
• Pregnancy Complications/prevention & control
• Zinc/metabolism

Wilson's disease (WD) is a rare genetic disorder of copper metabolism that often manifests several clinical signs at the time of diagnosis. Typically it affects the liver in the early stages of the disease course and tends to show neuropsychiatric involvement in the later stages. Early diagnosis of WD holds a prognostic value, and an atypical presentation of the disease adds complexities in diagnosis. Even though we need to consolidate further the treatment guidelines for managing psychiatric and neurological symptoms optimally in the patients of WD, identifying signs at the early stages of the disease is crucial to avoid its detrimental effects on the human body. In this case presentation, a patient with no family history of psychiatric condition showed an early onset of neuropsychiatric symptoms without any other clinical signs of WD. Through this clinical case, we emphasize the importance of ruling out WD in patients that predominantly presents with psychiatric symptoms as a lone symptom. It also highlights the possible diagnostic value and significance of the ceruloplasmin level in identifying WD disease in early stages, when other clinical signs are absent, including liver abnormalities.

• ceruloplasmin
• hepatomegaly
• kayser fleischer ring
• kayser-fleischer ring
• neuropsychiatry
• psychosis
• wilson's disease

• CRISPR/Cas9
• DNA
• Gene therapy
• gene editing
• gene expression
• gene silencing
• guide RNA (gRNA)
• hepatocyte
• lipid nanoparticle (LNP)
• lipids
• liver
• messenger RNA (mRNA)
• small interfering RNA (siRNA)

• Animals
• Gene Expression Regulation
• Gene Transfer Techniques
• Genetic Therapy
• Humans
• Lipids/administration & dosage
• Liver/metabolism
• Nanoparticles/administration & dosage
• Nanotechnology

• AAV
• ATP7B
• Wilson's disease
• gene therapy

• Copper toxicity
• HIF-1 signaling
• Steatosis
• Wilson's disease
• Zebrafish

• Animals
• CRISPR-Cas Systems
• Copper/metabolism
• Copper/toxicity
• Copper-Transporting ATPases/genetics
• Disease Models, Animal
• Fatty Liver/genetics
• Fatty Liver/metabolism
• Fatty Liver/pathology
• Female
• Gene Knockout Techniques
• Hep G2 Cells
• Hepatocytes/metabolism
• Hepatolenticular Degeneration/genetics
• Hepatolenticular Degeneration/metabolism
• Humans
• Hypoxia-Inducible Factor 1/metabolism
• Liver/metabolism
• Liver/pathology
• Male
• Mutation
• Signal Transduction/physiology
• Zebrafish
• Zebrafish Proteins/genetics

• Ataxia
• Chorea gravidarum
• Dystonia
• Huntington disease
• Parkinson disease
• Restless legs syndrome
• Tourette syndrome
• Tremor
• Wilson disease

• Dystonia
• Essential Tremor
• Female
• Hepatolenticular Degeneration
• Humans
• Huntington Disease
• Movement Disorders/diagnosis
• Movement Disorders/etiology
• Movement Disorders/therapy
• Parkinson Disease
• Pregnancy

• acute onset
• emotional stimulation
• mild trauma
• neurological symptoms
• surgery
• wilson disease

• Adolescent
• Adult
• Brain/diagnostic imaging
• Child
• Cross-Sectional Studies
• Emotions
• Female
• Follow-Up Studies
• Hepatolenticular Degeneration/drug therapy
• Hepatolenticular Degeneration/epidemiology
• Hepatolenticular Degeneration/physiopathology
• Humans
• Male
• Middle Aged
• Pilot Projects
• Postoperative Complications/epidemiology
• Proof of Concept Study
• Retrospective Studies
• Stress, Psychological/complications
• Stress, Psychological/epidemiology
• Time Factors
• Young Adult

• Wilson disease
• infant
• maternal and foetal outcome
• pregnancy

• ATP7B
• Chinese herbal medicine
• Wilson's disease
• anti-oxidation
• systematic review

The clinical effect of copper accumulation on the heart of patients suffering from Wilson’s disease (WD) is not completely understood. We aimed to determine if patients with WD show signs of cardiac involvement, structural heart disease or autonomic dysfunction. In this prospective trial, we studied 61 patients (mean age 44.3 ± 15.2 years, 51% males) with WD and compared them to 61 age- and gender-matched healthy controls. All subjects underwent clinical examination, blood tests, echocardiography and 24 h electrocardiographic (ECG) recording.

Left- and right ventricular systolic function did not differ significantly between WD patients and controls. However, 5 of the 61 patients had a reduced left ventricular ejection fraction (LVEF). Furthermore, diastolic dysfunction was more prevalent in WD patients (9 of 61 vs. 0 of 61, p = 0.001).

The severity of WD based on the Unified Wilson’s Disease Rating Scale was significantly correlated to NT-pro BNP (r = 0.34, P = 0.013). Patients with an exacerbation of WD in medical history had higher troponin levels compared to those without (11.3 ± 4.7 vs 4.6 ± 1.2).

The autonomic function assessed by triangular index (TI) and SDNN-index was significantly reduced in WD patients compared to controls in most in almost every age category (p-value TI and SDNN: age 20–29, p < 0.001 and 0.05; age 30–39, p < 0.01 and not significant (ns); age 40–49, p < 0,01 and 0.001; age 50–59, p = ns and < 0.001, age 60–70, p < 0.05 and ns).

Our data demonstrate that cardiac involvement and autonomic dysfunction in WD is possible, however the underlying cause is still not known. We suggest that patients with signs and symptoms of structural heart disease should be examined by a cardiologist in addition to the interdisciplinary treatment team of WD.

The online version of this article (10.1186/s13023-019-1007-7) contains supplementary material, which is available to authorized users.

• Autonomic dysfunction
• Cardiac involvement
• Echocardiography
• Heart failure
• Unified Wilson’s disease rating scale
• Wilson’s disease

• AASLD, American Association for the Study of Liver Diseases
• ACLF, Acute on Chronic Liver Failure
• ALF, Acute Liver Failure
• ALT, Alanine Transaminase
• AST, Aspartate Transaminase
• Cu, Copper
• DP, D-Penicillamine
• EASL, European Association for the Study of the Liver
• GAS for WD, Global Assessment Scale for Wilson's Disease
• HCC, Hepatocellular Carcinoma
• INR, International Normalized Ratio
• KF, Kayser-Fleischer
• LT, Liver Transplantation
• MARS, Molecular Absorption Recirculating System
• MELD, Model for End-Stage Liver Disease
• MRI, Magnetic Resonance Imaging
• NGS, Next-Generation Sequencing
• NWI, New Wilson's Index
• PELD, Pediatric end stage liver disease
• TPE, Total Plasma Exchange
• TTM, Tetrathiomolybdate
• WD, Wilson's Disease
• Wilson's disease scoring
• genetic disorder
• modified Leipzig scoring
• rare disease

• wilson disease
• gene expression
• transcription network
• zinc
• copper
• homeostasis
• metalloprotein

• Animals
• Copper/toxicity
• Copper-Transporting ATPases/physiology
• Disease Models, Animal
• Gene Regulatory Networks
• Hepatolenticular Degeneration
• Liver/drug effects
• Liver/metabolism
• Liver/pathology
• Metallothionein/metabolism
• Mice
• Mice, Knockout
• Zinc/metabolism

• P30 EY010572 NEI NIH HHS
• R15 DK114747 NIDDK NIH HHS
• S10 RR025512 NCRR NIH HHS
• P20 GM103451 NIGMS NIH HHS
• R01 GM090016 NIGMS NIH HHS
• P30 CA069533 NCI NIH HHS
• P20 GM103395 NIGMS NIH HHS
• R01 DC002368 NIDCD NIH HHS

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.

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.

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.

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.

• Liver
• Macrophages
• Metabolic liver function
• Wilson disease
• sCD163

• Animal models
• Wilson disease

• Animals
• Animals, Genetically Modified
• Copper-Transporting ATPases/deficiency
• Copper-Transporting ATPases/genetics
• Copper-Transporting ATPases/metabolism
• Disease Models, Animal
• Hepatolenticular Degeneration/genetics
• Hepatolenticular Degeneration/therapy
• Humans
• Mutation/genetics

• R01 DK071865 NIDDK NIH HHS
• R01 GM101502 NIGMS NIH HHS

• LDLT, living donor liver transplantation
• MELD, model for end-stage liver disease
• WD, Wilson's disease
• Wilson's disease
• complications
• living donor liver transplantation
• survival

• Biliary atresia
• Ceruloplasmin
• Cholestasis
• Hepatic Cu
• Infants
• Intrahepatic cholestasis
• Serum Cu

• Biliary Atresia/complications
• Ceruloplasmin/metabolism
• Cholestasis, Intrahepatic/blood
• Cholestasis, Intrahepatic/diagnosis
• Cholestasis, Intrahepatic/etiology
• Copper/blood
• Copper/metabolism
• Hepatitis/diagnosis
• Hepatitis/etiology
• Hepatitis/prevention & control
• Humans
• Infant
• Liver/metabolism
• Liver/pathology
• Male
• Predictive Value of Tests
• Prognosis
• ROC Curve
• Sensitivity and Specificity
• Statistics as Topic

• Adolescent
• Adult
• Anticonvulsants/therapeutic use
• Brain Diseases/chemically induced
• Female
• Headache/chemically induced
• Hepatolenticular Degeneration/complications
• Hepatolenticular Degeneration/diagnosis
• Hepatolenticular Degeneration/genetics
• Humans
• Immunosuppressive Agents/adverse effects
• Liver Failure/diagnosis
• Liver Failure/etiology
• Liver Failure/surgery
• Liver Transplantation/adverse effects
• Male
• Medical Records
• Nervous System Diseases/chemically induced
• Nervous System Diseases/diagnosis
• Nervous System Diseases/therapy
• Retrospective Studies
• Risk Factors
• Seizures/chemically induced
• Seizures/drug therapy
• Time Factors
• Treatment Outcome
• Tremor/chemically induced
• Turkey
• Young Adult

A 64-year-old woman, presented with abdominal distention, jaundice and resting tremor, was found to have liver injury and abnormal liver enzymes. A computed tomography (CT) scan of the abdomen and pelvis showed abdominopelvic ascites and signs of liver cirrhosis. An extensive liver disease workup was performed and came back negative; therefore, a liver biopsy was obtained and showed evidence of cirrhosis with elevated liver copper consistent with Wilson’s disease (WD). We report a unique case of late-onset WD in which the ceruloplasmin level and 24-h urinary copper excretion were all normal.

• ceruloplasmin
• copper
• liver