Wilson disease is a rare genetic disease characterized by the excessive accumulation of copper in the body tissues and organs, primarily the liver and brain.1 Mutations in the copper-transporting gene, ATP7B, which codes for a copper-transporting protein located mostly in the liver and brain, are responsible for the development of Wilson disease.1 The disease can result in death due to liver failure or complications deriving from neurological symptoms.2 

Wilson disease can be managed through the removal of copper from the body tissues and blood using copper chelation or by using zinc salts to prevent the absorption of copper.2 There are, however, patients who do not respond to these therapeutic approaches and are candidates for a liver transplant, as this disease primarily affects the liver.2,3 

Liver Transplantation in Wilson Disease

Liver transplantation is a curative strategy in the management of Wilson disease. It is considered a phenotypic correction of the faulty gene responsible for the development of disease, and it is expected to restore copper excretion and absorption.2,3 Current guidelines suggest that patients with Wilson disease who present with acute liver failure with encephalopathy should undergo urgent liver transplantation.4 Transplantation on patients with neurological disease who do not have liver damage is still matter of debate, however, reports show improvements in neurological symptoms following transplant.2

Read more about Wilson disease treatment

Liver transplantation is currently indicated for patients with Wilson disease who present with acute liver failure, which typically affects about 5% of patients, or decompensated liver cirrhosis that does not respond to pharmacological treatment.2,3 The indication for transplant is based on a Wilson disease clinical scale for the prediction of survival among patients not undergoing surgery, typically the revised King’s prognostic Wilson Index.1,4 This New Wilson Index (NWI) accounts for serum bilirubin levels, white blood cell count, INR, and aspartate aminotransferase levels, and it indicates mortality without transplantation with scores of 11 or higher.4,5

Options for liver transplantation include living liver donation, cadaveric orthotopic transplant, and auxiliary transplantation.6

Preparing for a Liver Transplantation

There are supportive measures that can be considered while patients wait for surgery.6 In patients with acute liver failure, treatment is focused on decreasing excessive serum copper levels to reduce complications such as infection, acute kidney injury, intracranial hypertension, and further damage to the liver.2,6 Acute liver failure can cause a rapid increase in copper in the blood, leading to acute hemolysis and allowing copper to enter the brain.3 Reducing the concentration of copper in the serum of these patients can be achieved with exchange transfusion, plasmapheresis, hemofiltration, albumin dialysis, and molecular adsorbent recirculating system (MARS). Renal failure can also be observed, which typically does not respond to penicillamine or trientine due to reduced renal clearance.2 

Patients with chronic liver failure should be monitored for complications of portal hypertension, as well as for esophageal and gastric varices. Sodium restriction and the use diuretics should be considered.2

Outcomes of Liver Transplantation

Excellent outcomes are observed in adult and pediatric patients with Wilson disease undergoing liver transplantation. Complications associated with portal hypertension and neurological symptoms have been also shown to improve after surgery.2 There are, however, patients who do not recover from neurological symptoms.2 In fact, following liver transplantation, paradoxical neurological deterioration may be observed, and anesthetics can also lead to neurological deterioration.3

References

1. Poujois A, Woimant F. Wilson’s disease: a 2017 update. Clin Res Hepatol Gastroenterol. 2018;42(6):512-520. doi:10.1016/j.clinre.2018.03.007

2. Schilsky ML. Liver transplantation for Wilson’s disease. Ann N Y Acad Sci. 2014;1315:45-49. doi:10.1111/nyas.12454

3. Członkowska A, Litwin T, Dusek P, et al. Wilson disease. Nat Rev Dis Primers. 2018;4(1):21. doi:10.1038/s41572-018-0018-3

4. Nagral A, Sarma MS, Matthai J, et al. Wilson’s disease: clinical practice guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India. J Clin Exp Hepatol. 2019;9(1):74-98. doi:10.1016/j.jceh.2018.08.009

5. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transpl. 2005;11(4):441-448. doi:10.1002/lt.20352

6. Ahmad A, Torrazza-Perez E, Schilsky ML. Liver transplantation for Wilson disease. Handb Clin Neurol. 2017;142:193-204. doi:10.1016/B978-0-444-63625-6.00016-1

Reviewed by Kyle Habet, MD, on 9/29/2022.

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