EASL Clinical Practice Guidelines

Introduction

Normal dietary consumption and absorption of copper exceed the metabolic need, and homeostasis of this element is maintained exclusively by the biliary excretion of copper. Wilson's disease is an inherited disorder in which defective biliary excretion of copper leads to its accumulation, particularly in liver and brain [[1], [2]]. Wilson's disease is due to mutations of the ATP7B gene on chromosome 13 [[3], [4]], which encodes a copper-transporting P-type ATPase (ATP7B) residing in the trans-Golgi network of hepatocytes. ATP7B is responsible for transporting copper from intracellular chaperone proteins into the secretory pathway, both for excretion into bile and for incorporation into apo-ceruloplasmin for the synthesis of functional ceruloplasmin [[3], [4]]. The development of Wilson's disease is due to the accumulation of copper in affected tissues.

Table 1
(A) GRADE system as used in EASL Clinical Practice Guidelines [159]. (B) System of Recommendations as used in AASLD Practice Guidelines [130].

Clinical presentation can vary widely, but the key features of Wilson's disease are liver disease and cirrhosis, neuropsychiatric disturbances, Kayser–Fleischer rings in Desçemet's membrane of the cornea, and acute episodes of hemolysis often in association with acute liver failure. Wilson's disease is not just a disease of children and young adults, but may present at any age [5].

Wilson's disease is a genetic disorder that is found worldwide. Wilson's disease is recognized to be more common than previously thought, with a gene frequency of 1 in 90–150 and an incidence (based on adults presenting with neurologic symptoms [6]) that may be as high as 1 in 30,000 [7]. More than 500 distinct mutations have been described in the Wilson gene, from which 380 have a confirmed role in the pathogenesis of the disease [8].