The prognosis for patients with untreated Wilson disease is poor; the median life expectancy is 40 years, with most patients dying of liver disease and a minority dying of complications of progressive neurological disease. However, a normal life expectancy can be achieved if the disease is diagnosed early and treated in a timely manner with currently available therapies and liver transplant, if recommended.1 Appropriate life-long pharmacological treatment significantly decreases neurological and hematological symptoms. However, little improvement is seen in patients with impaired liver function due to cirrhosis and complications of portal hypertension. In these cases, a liver transplant is necessary if normal hepatic copper excretion is to be restored and can be life-saving. Current therapies for neurological symptoms are usually not effective; the symptoms are only partially reversed and in rare cases may progress further.1

Factors Affecting Prognosis

In general, a patient’s outcome depends on the severity of liver and neurological disease and compliance with drug treatment. In most patients who present with no or compensated cirrhosis, liver function recovers to normal with 1-2 years of medication therapy. However, in patients presenting with acute liver failure due to Wilson disease, medical therapy is rarely effective. Liver transplant may be indicated for those patients with acute liver failure on the basis of their score on the revised King’s Wilson prognostic index.2,3 A score of 11 or higher suggests a high probability of death without transplant.4

Liver Transplant

The prognosis of patients after liver transplant is satisfactory. In 2 follow-up studies that assessed patient outcome after orthotopic liver transplant,5,6 the 1-year survival rate was 79% and the maximum survival time was 20 years. Survival was better among the patients who had chronic advanced liver cirrhosis than among those with acute liver failure.

Liver Transplant in Children

In a recent systematic review of 290 pediatric patients (younger than 18 years), long-term patient outcomes after liver transplant were excellent and likely better than those of adults after liver transplant. The average 1-year survival rate for children with a liver transplant was 91.9%, and the 5-year survival rate was 88.2%.7

Early Diagnosis

An early diagnosis is critical to reduce liver and brain damage and prevent disability and early death. Asymptomatic patients can be identified with family screening so that treatment can be started before clinical symptoms appear. In children younger than 3 years, the results of genetic sequencing are more reliable than decreased serum ceruloplasmin levels, which are generally similar to those of adults by the age of 3.8

The importance of early diagnosis and treatment in improving the prognosis of patients with Wilson disease was assessed in a study of 87 asymptomatic patients in whom the disease was diagnosed early through family screening and who were treated with anti-copper agents (zinc sulfate and penicillamine). The majority of these patients (63%) had a good outcome, with no development of disease and overall survival similar to that of healthy people. The study also showed that patient compliance with therapy is necessary for a good outcome; the odds of the development of symptomatic Wilson disease were increased among those who did not comply with therapy.9

Persistence With Therapy

In a study of 170 patients with newly diagnosed symptomatic Wilson disease, persistence with treatment was shown to be critical to long-term prognosis. Worsening disease was more frequent in the patients who did not persist with therapy than in those who did.10

References

  1. Stremmel W, Weiskirchen R. Therapeutic strategies in Wilson disease: pathophysiology and mode of action. Ann Transl Med. 2021;9(8):732. doi:10.21037/atm-20-3090
  2. Nazer H, Ede RJ, Mowat AP, Williams R. Wilson’s disease: clinical presentation and use of prognostic index. Gut. 1986;27(11):1377-1381. doi:10.1136/gut.27.11.1377
  3. 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
  4. European Association for Study of Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56(3):671-685. doi:10.1016/j.jhep.2011.11.007
  5. 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
  6. Bellary S, Hassanein T, Van Thiel DH. Liver transplantation for Wilson’s disease. J Hepatol. 1995;23(4):373-381. doi:10.1016/0168-8278(95)80194-4
  7. Garoufalia Z, Prodromidou A, Machairas N, et al. Liver transplantation for Wilson’s disease in non-adult patients: a systematic review. Transplant Proc. 2019;51(2):443-445. doi:10.1016/j.transproceed.2019.01.017
  8. Yuan XZ, Yang RM, Wang XP. Management Perspective of Wilson’s Disease: Early Diagnosis and Individualized Therapy. Curr Neuropharmacol. 2021;19(4):465-485. doi:10.2174/1570159X18666200429233517
  9. Dzieżyc K, Karliński M, Litwin T, Członkowska A. Compliant treatment with anti-copper agents prevents clinically overt Wilson’s disease in pre-symptomatic patients. Eur J Neurol. 2014;21(2):332-337. doi:10.1111/ene.12320
  10. Masełbas W, Członkowska A, Litwin T, Niewada M. Persistence with treatment for Wilson disease: a retrospective study. BMC Neurol. 2019;19(1):278. doi:10.1186/s12883-019-1502-4

Reviewed by Harshi Dhingra, MD, on 10/4/2022.

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