Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease.

OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.

Characteristics and prevalence of Wilson's disease: A 2013 observational population-based study in France.

BACKGROUND AND AIMS: Only a few epidemiological studies on the incidence and prevalence of Wilson's disease (WD) have been performed to date, and the results vary widely according to the reports. The aim of the study was to investigate the prevalence, ambulatory care and treatments of patients with WD in France. METHODS: Among the 58 million general health scheme beneficiaries (86% of the French population), people managed for WD in 2013 were identified using hospitalisation diagnosis in 2011-2013 or specific long-term disease status with a 100% reimbursement for specific healthcare in 2013. Data were derived from the Sniiram (National Health Insurance Information System database). Prevalence by age and sex were calculated. RESULTS: In 2013, 906 prevalent cases were identified, yielding a crude prevalence of 1.5 cases per 100,000; 1.65 per 100,000 in males and 1.44 per 100,000 in females. This prevalence is comparable to that reported in other population-based studies in European countries and to a study using a similar method. Almost 40% of patients were treated by D-penicillamine and 14.3% were treated by zinc acetate. Trientine, delivered on a compassionate basis, was not available in the reimbursement database. In 2013, 1.3% of patients underwent liver transplantation and 4% had already undergone liver transplantation in previous years. Fifteen per cent of patients received antidepressants, a higher rate than in general population. CONCLUSIONS: This is the first French population-based epidemiological study of WD in a comprehensive population based on administrative data and constitutes an important step to understand the impact of WD and to study quality of care.

Bioavailable Trace Metals in Neurological Diseases.

OPINION STATEMENT: Medical treatment in Wilson's disease includes chelators (D-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators' doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron.

[Wilson disease]. / Maladie de Wilson.

UNLABELLED: Wilson Disease must be considered in very varied circumstances, including in patients older than 50 years. Its diagnosis is not based on a single test but on a group of findings. The copper levels may be difficult to interpret. Molecular biology can confirm the diagnosis in only 80% of cases. The advice of the reference center is necessary before beginning treatment: chelators or zinc salts. Lifetime treatment is required. Follow-up of these patients must be regular and multidisciplinary and should be conducted in association with the reference center. Inclusion in the national registry for Wilson Disease must be suggested to all patients. CONTACT: cmr.wilson@lrb.aphp.fr.