Liver and intrahepatic bile ducts-nontumor
Metabolic diseases
Wilson's disease

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

Revised: 11 May 2016, last major update April 2012

Copyright: (c) 2004-2016, PathologyOutlines.com, Inc.

PubMed Search: Wilson's disease[title] liver
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
  • The gene for Wilson’s 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 micrograms/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 micrograms/24 hours
  • Case Reports
  • 8 year old boy with acute liver failure (Case of the Week #388)
  • Treatment
  • Long-term copper chelation therapy with D-penicillamine
  • Liver transplantation
  • Micro Description
  • Liver: fatty change with vacuolated nucleus (due to glycogen or water), focal hepatocyte necrosis
  • An 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’s membrane in limbus of cornea)
  • Micro 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
  • Copper accumulation also present in primary biliary cirrhosis, other cholestatic states