Liver transplantation for Wilson disease

Ahmad, Ahsan; Torrazza-Perez, Euriko; Schilsky, Michael L.

doi:10.1016/b978-0-444-63625-6.00016-1

Cited by 34 publications

(23 citation statements)

References 57 publications

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“…Liver transplantation early in disease management remains a controversial issue. 44 Medical therapy for individual movement disorders can also be used and deep brain stimulation has been reported as beneficial for severe tremor and dystonia in patients with Wilson disease. 45…”

Section: Wilson Diseasementioning

confidence: 99%

Movement Disorders and Neurometabolic Diseases

Christensen

Walsh

2018

Seminars in Pediatric Neurology

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Many inherited metabolic diseases or inborn errors of metabolism (IEM) cause movement disorders in children. This review focuses on chorea, dystonia, myoclonus, tremor, and parkinsonism. Broad neurometabolic categories commonly responsible for pediatric movement disorders include mitochondrial cytopathies, organic acidemias, mineral metabolism and transport disorders, neurotransmitter diseases, purine metabolism abnormalities, lipid storage conditions, and creatine metabolism dysfunction. Each movement disorder can be caused by many IEM and several of them can cause multiple movement abnormalities. Dietary modifications, medications, and increasingly specific therapy can improve outcomes in children with movement disorders caused by IEM. Recognition and characterization of secondary movement disorders in children facilitate their management and diagnosis, and possible treatment of an underlying IEM.

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Section: Wilson Diseasementioning

confidence: 99%

Movement Disorders and Neurometabolic Diseases

Christensen

Walsh

2018

Seminars in Pediatric Neurology

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“…However, several studies have suggested that patients with prior neuropsychiatric symptoms had worse outcomes after LT in terms of postoperative complications and survival (16) and that the total reversibility of their symptoms could not be achieved. (12,(17)(18)(19)(20)(21) The feasibility of extending LT to WD patients with both severe neurological impairments and compensated liver disease, which had remained merely theoretical for decades, (22,23) has also recently been highlighted. (24) A multicenter observational study previously analyzed the clinical scenario of LT for WD in Italy between 1985 and 2005.…”

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confidence: 99%

Outcomes of Liver Transplant for Adults With Wilson’s Disease

et al. 2020

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Wilson’s disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end‐stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19‐60 years]; median Model for End‐Stage Liver Disease score at LT, 27 [6‐49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1‐ and 5‐year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post‐LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.

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“…If Wilson's disease is diagnosed in the early, presymptomatic phase, the prognosis is good with current therapeutics. Nevertheless, early diagnosis is challenging, and treatment becomes more difficult as the course of the disease progresses; ultimately, patients may develop fulminant hepatic failure that requires liver transplantation for resolution (Ahmad et al 2017;Boga et al 2017). The primary therapeutic strategy is to try to reduce the levels of copper in the patient and re-establish homeostasis.…”

Section: Discussionmentioning

confidence: 99%

DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson's disease

et al. 2018

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The levels of copper, which is an essential element in living organisms, are under tight homeostatic control. Inactivating mutations in ATP7B, a P-type Cu-ATPase that functions in copper excretion, promote aberrant accumulation of the metal, primarily the in liver and brain. This condition underlies Wilson's disease, a severe autosomal recessive disorder characterized by profound hepatic and neurological deficits. Current treatment regimens rely on the use of broad specificity metal chelators as "decoppering" agents; however, there are side effects that limit their effectiveness. Here, we present the characterization of DPM-1001 {methyl 4-[7-hydroxy-10,13-dimethyl-3-({4-[(pyridin-2-ylmethyl)amino]butyl}amino)hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl] pentanoate} as a potent and highly selective chelator of copper that is orally bioavailable. Treatment of cell models, including fibroblasts derived from Wilson's disease patients, eliminated adverse effects associated with copper accumulation. Furthermore, treatment of the toxic milk mouse model of Wilson's disease with DPM-1001 lowered the levels of copper in the liver and brain, removing excess copper by excretion in the feces while ameliorating symptoms associated with the disease. These data suggest that it may be worthwhile to investigate DPM-1001 further as a new therapeutic agent for the treatment of Wilson's disease, with potential for application in other indications associated with elevated copper, including cancer and neurodegenerative diseases.

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Liver transplantation for Wilson disease

Cited by 34 publications

References 57 publications

Movement Disorders and Neurometabolic Diseases

Movement Disorders and Neurometabolic Diseases

Outcomes of Liver Transplant for Adults With Wilson’s Disease

DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson's disease

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