Wilson disease is a rare disorder with autosomal-recessive inheritance that is characterized by the excessive accumulation of copper throughout the tissues, especially those of the liver, brain, and eyes.1 

Genetic mutations of the ATP7B gene result in the formation of abnormal ATP7B protein, which results in the sequestration of excess copper in the liver and impairs its secretion into the biliary system. The incorporation of copper into ceruloplasmin in the liver is also impaired. These abnormalities result in an excessive accumulation of copper within hepatocytes and eventual overflow into the blood, with the deposition of excess copper in other tissues and excretion in the urine.2 

Liver Transplant

In most patients with Wilson disease, hepatic symptoms usually manifest first, as a consequence of hepatocellular injury.2 Orthotopic liver transplant is a curative treatment for Wilson disease, after which serum ceruloplasmin levels return to normal, the urinary excretion of copper decreases, and hepatic and neurological symptoms decrease.3

The first indication for liver transplant is acute liver failure, which occurs in 5% of all individuals with Wilson disease.4 In a study published in 2002, acute liver failure due to Wilson disease accounted for between 4% and 6% of all liver transplants in the United States.5 

The second indication for liver transplant is chronic liver disease that has progressed to cirrhosis and portal hypertension in a patient with Wilson disease that no longer responds to chelating agents or was not diagnosed or treated in a timely manner.4

Several studies reported 1- and 5- year overall survival rates above 85% in patients with Wilson disease who underwent successful liver transplant.4,6-8 Survival rates at 1 and 5 years were slightly higher in children and adults with chronic liver disease secondary to Wilson disease than in children and adults with fulminant hepatic failure.7

Liver transplant has been shown to reverse neurological deterioration in patients with Wilson disease. One study reported that neurological symptoms decreased or stabilized in 78% of 41 patients following liver transplant,9 whereas another study reported total or partial neurological improvement in 58.8% of 17 patients.10   

Many treatments are available for the management of Wilson disease and acute liver failure in patients who are waiting for a liver transplant. Treatments such as exchange transfusion, plasmapheresis, fractionated plasma separation and absorption (FPSA), the molecular adsorbent recycling system (MARS), albumin dialysis, and renal replacement therapy decrease levels of circulating copper, reduce hemolysis, improve renal and hepatic function, and potentially influence transplant outcomes.4 

Pharmacological Treatments

Wilson disease requires lifelong pharmacological management focused on decreasing copper overload—either by removing or detoxifying copper deposited in the tissues or by preventing further accumulation of copper.11  

Penicillamine, a chelating agent, is a heavy metal antagonist that binds excess copper in the body and promotes its excretion through the urine.12 Trientine is a copper chelator that reduces the intestinal absorption of copper and promotes urinary excretion.13 Zinc acetate (Galzin®) blocks the intestinal absorption of copper through the induction of intestinal cell metallothionein. Zinc is less toxic than other anticopper agents used to treat Wilson disease.14 Patients who do not tolerate penicillamine or trientine because of toxic side effects may use zinc acetate as their primary therapy.15 

Patients with Wilson disease require long-term monitoring of their copper and zinc levels to avoid overtreatment and copper deficiency, especially children who are still growing.14

Additional pharmaceutical treatments may be used to alleviate neurological symptoms caused by Wilson disease, including tremors, parkinsonism, dystonia, and chorea.16

References

  1. Wilson disease. Medline Plus. Accessed September 9, 2022.
  2. Gilroy RK. Wilson disease: etiology. Medscape. Updated February 14, 2019. Accessed September 9, 2022.
  3. Sevmis S, Karakayali H, Aliosmanoglu I, et al. Liver transplantation for Wilson’s disease. Transplant Proc. 2008;40(1):228-230. doi:10.1016/j.transproceed.2007.11.007
  4. Catana AM, Medici V. Liver transplantation for Wilson disease. World J Hepatol. 2012;4(1):5-10. doi:10.4254/wjh.v4.i1.5
  5. Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137(12):947-954. doi:10.7326/0003-4819-137-12-200212170-00007
  6. Schilsky ML. Diagnosis and treatment of Wilson’s disease. Pediatr Transplant. 2002;6(1):15-19. doi:10.1034/j.1399-3046.2002.1r069.x
  7. Arnon R, Annunziato R, Schilsky M, et al. Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults. Clin Transplant. 2011;25(1):E52-E60. doi:10.1111/j.1399-0012.2010.01327.x
  8. Sutcliffe RP, Maguire DD, Muiesan P, et al. Liver transplantation for Wilson’s disease: long-term results and quality-of-life assessment. Transplantation. 2003;75(7):1003-1006. doi:10.1097/01.TP.0000055830.82799.B1
  9. Stracciari A, Tempestini A, Borghi A, Guarino M. Effect of liver transplantation on neurological manifestations in Wilson disease. Arch Neurol. 2000;57(3):384-386. doi:10.1001/archneur.57.3.384
  10. Eghtesad B, Nezakatgoo N, Geraci LC, et al. Liver transplantation for Wilson’s disease: a single-center experience. Liver Transpl Surg. 1999;5(6):467-474. doi:10.1002/lt.500050614
  11. Schilsky ML. Wilson disease: treatment and prognosis. UpToDate. Updated September 8, 2022. Accessed September 9, 2022.
  12. Penicillamine. MedlinePlus Drug Information. Accessed September 9, 2022.
  13. Trientine – an overview. ScienceDirect. Accessed September 9, 2022.
  14. Brewer GJ. Zinc acetate for the treatment of Wilson’s disease. Expert Opin Pharmacother. 2001;2(9):1473-1477. doi:10.1517/14656566.2.9.1473
  15. Wilson disease: diagnosis and treatment. Mayo Clinic. Accessed September 9, 2022.
  16. Litwin T, Dušek P, Członkowska A. Symptomatic treatment of neurologic symptoms in Wilson disease. Handb Clin Neurol. 2017;142:211-223. doi:10.1016/B978-0-444-63625-6.00018-5

Reviewed by Harshi Dhingra, MD, on 9/15/2022.

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