Wilson disease, a rare, inherited disorder of copper metabolism that typically manifests with varying degrees of symptom severity between the ages of 5 and 35 years; however, symptoms of the condition may appear at any age.1 The accumulation of excess copper within the liver and brain may result in fatal disease complications such as liver failure, cirrhosis, or the development of malignant disease.2,3 

Death typically occurs due to liver, kidney, or hematologic complications related to Wilson disease. Patients with cirrhosis who develop portal hypertension and varices in the esophagus and stomach are prone to bleeding, which increases the risk of death.4

One study that analyzed the cause of death in 300 patients with Wilson disease between 1948 and 2000 reported that the principal cause of death was diagnostic failure followed by a lack of adherence to treatment recommendations and the development of malignancies after 10 years of follow-up. Prior to 1948, all patients died shortly after diagnosis, which typically occurred following the manifestation of neurological symptoms late in the natural disease course.3 

Depending on how rapidly the disease progresses and the age of onset, patients may live up to 40 years without treatment, but ultimately, untreated Wilson disease is always fatal.1,2 Typically, early diagnosis and prompt treatment initiation may result in normal life spans for patients with Wilson disease. An early onset of Wilson disease typically correlates with a worse prognosis. If left untreated or if a patient discontinues treatment with chelators, the disease may result in rapid deterioration and mortality within 1 to 3 years.4 

Prognostic Indicators

In one study, a cohort of 229 patients with Wilson disease demonstrated a lower 20-year survival rate than the healthy Austrian population (92% vs 97%; P =.03). This cohort presented with a wide range of manifestations, including hepatic disease (61%), neurological symptoms (27%), and asymptomatic presentation upon family screening (10%). Most patients improved (24%), stabilized (35%), or completely recovered (26%) following chelation therapy, while the remaining 15% declined, with 8% requiring liver transplantation and 7.4% dying during the long study period.5 

In this cohort, cirrhosis was the best predictor of mortality, followed by the need for liver transplantation. Compared with healthy Austrians, 84% of patients with Wilson disease who had cirrhosis survived 20 years after diagnosis (P =.008).5

The Nazer score predicts the risk of mortality at the time of diagnosis by analyzing serum aspartate aminotransferase (AST) levels, bilirubin levels, and prolongation of prothrombin time (international normalized ratio; INR). Nazer scores range from 0 to 12, with scores ≤6 predicting patient responsiveness to chelation therapy.4,6 

Dhawan and colleagues improved the Nazer score (also known as the King’s score) by adding albumin and white blood cell levels to the scoring system. Scores >11 predicted patient death without liver transplantation, while scores ≤11 predicted favorable patient response to chelation therapy.6,7

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Liver Transplantation

Patients with Wilson disease who undergo liver transplantation have a good prognosis. One study reported a 1-year survival rate of 79% and an overall survival rate of 72% after 20 years in 55 patients with Wilson disease following liver transplantation.8,9 

Another study reported 1-, 5-, and 10-year survival rates of 90.6%, 83.7%, and 79.9%, respectively, in 32 patients with Wilson disease after liver transplantation.8,10 

A recent systematic review of the literature summarized 48 studies, which revealed that liver transplantation significantly improved the outcomes of 71.2% of 215 patients with Wilson disease who presented with neurological symptoms. In the remaining patients, neurological symptoms either remained unchanged (6.9%) or worsened (7.9%), while 9.6% of patients died and 4.3% were lost to follow-up.11

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References

  1. Living with Wilson disease. Wilson Disease Association. Accessed September 16, 2022.
  2. Sruthi M. What is the life expectancy of a person with Wilson’s disease? MedicineNet. Accessed September 16, 2022.
  3. Walshe JM. Cause of death in Wilson disease. Mov Disord. 2007;22(15):2216-2220. doi:10.1002/mds.21693
  4. Kapur T. Wilson’s disease – outlook (prognosis). Medindia. April 22, 2013. Updated February 13, 2018. Accessed September 16, 2022. 
  5. Beinhardt S, Leiss W, Stättermayer AF, et al. Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clin Gastroenterol Hepatol. 2014;12(4):683-689. doi:10.1016/j.cgh.2013.09.025
  6. Rosencrantz R, Schilsky M. Wilson disease: pathogenesis and clinical considerations in diagnosis and treatment. Semin Liver Dis. 2011;31(3):245-259. doi:10.1055/s-0031-1286056
  7. 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
  8. Gilroy RK. Wilson disease: prognosis. Medscape. Updated February 14, 2019. Accessed September 16, 2022.
  9. Schilsky ML, Scheinberg IH, Sternlieb I. Liver transplantation for Wilson’s disease: indications and outcome. Hepatology. 1994;19(3):583-587. doi:10.1002/hep.1840190307
  10. Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson’s disease after living-donor liver transplantation. Transplantation. 2009;87(2):261-267. doi:10.1097/TP.0b013e3181919984
  11. Litwin T, Bembenek J, Antos A, et al. Liver transplantation as a treatment for Wilson’s disease with neurological presentation: a systematic literature review. Acta Neurol Belg. 2022;122(2):505-518. doi:10.1007/s13760-022-01872-w

Reviewed by Kyle Habet, MD, on 9/27/2022.

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