Liver and intrahepatic bile ducts-nontumor
Metabolic diseases
Wilson disease

Author: Komal Arora, M.D. (see Authors page)

Revised: 30 October 2017, last major update April 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Wilson disease[TI] liver[TI]
Cite this page: Arora, K. Wilson disease. PathologyOutlines.com website. http://pathologyoutlines.com/topic/liverwilsonsdisease.html. Accessed December 14th, 2017.
Definition / general
  • Also called hepatolenticular degeneration
  • Autosomal recessive disorder affecting 1/30,000 people, causing accumulation of toxic levels of copper in tissues / organs, usually liver, brain, eye (Clin Gastroenterol Hepatol 2005;3:726)
Pathophysiology
  • Total body copper is 50 - 150 mg; 40% of ingested copper is normally absorbed in stomach and duodenum and transported to liver loosely bound to albumin
  • Free copper dissociates and is transferred to hepatocytes, where it is incorporated into an alpha2 globulin to form ceruloplasmin and resecreted into plasma
  • 99% of plasma copper is bound to ceruloplasmin
  • Senescent ceruloplasmin is endocytosed by the liver, degraded within lysosomes and excreted into bile, which is the primary route for copper elimination
  • Gene for Wilson disease is ATP7B on #13q, which encodes a transmembrane copper transporting ATPase located on the hepatocyte canalicular membrane, which assists with copper excretion into bile
  • Most affected patients are compound heterozygotes with different mutations of ATP7B on each allele that cause defective biliary excretion of copper
  • Copper accumulates within the liver, exceeding the capacity for ceruloplasmin binding and causing liver injury
Clinical features
  • By age 5 years, nonceruloplasmin bound copper causes acute or chronic liver disease, hemolytic anemia, deposition in putamen with frank psychosis or Parkinsonian symptoms, deposition in cornea, kidneys, bones, joints, parathyroid gland; also increased urinary excretion of copper (which is normally minimal)
  • Biochemical determination from liver biopsy (can use formalin fixed tissue, > 250 mcg/g dry weight)
  • Serum copper levels are not helpful
Diagnosis
  • Serum ceruloplasmin < 20 mg/dl, increased liver copper using rhodamine stain, urinary copper excretion > 50 mcg/24 hours
Case reports
Treatment
  • Longterm copper chelation therapy with D-penicillamine
  • Liver transplantation
Microscopic (histologic) description
  • Liver: fatty change with vacuolated nucleus (due to glycogen or water), focal hepatocyte necrosis
  • Acute or chronic hepatitis may be present and mimic acute or chronic viral hepatitis
  • Chronic hepatitis may have Mallory bodies
  • Cirrhosis develops late; usually no / minimal eosinophils or plasma cells
  • Note: copper deposition is focal and may not be present on needle biopsies
  • Fulminant hepatitis: liver collapse with abundant lipofuscin due to degraded membrane fragments; remaining liver shows low grade disease with fibrosis
  • Brain: injury to putamen in basal ganglia
  • Eye: Kayser-Fleischer rings (green to brown deposits of copper in Descemet membrane in limbus of cornea)
Microscopic (histologic) images

Images hosted on PathOut server:

Case of the Week #388:

Rhodanine stain for copper

Electron microscopy description
  • Microvesicular steatosis, glycogen nuclei, copper deposits, mitochondrial enlargement with increased matrical body size, increased matrix density, crystalline inclusions, swollen cristae that are separated due to flocculent material in cyst-like dilations
Differential diagnosis