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Metabolic diseases

Wilson disease


Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
ILKe Nalbantoglu, M.D.

Last author update: 15 March 2022
Last staff update: 15 March 2022

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PubMed Search: Wilson disease liver pathology[TIAB]

ILKe Nalbantoglu, M.D.
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Nalbantoglu I, DiDomenico P. Wilson disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverwilsonsdisease.html. Accessed June 9th, 2023.
Definition / general
  • Increased / toxic copper deposition within liver, cornea, kidney and central nervous system
  • Due to ATP7B mutation (absence or dysfunction of copper transporting ATPase)
  • Autosomal recessive
Essential features
ICD coding
  • ICD-10: E83.01 - Wilson disease
  • ICD-11: 5C64.00 - Wilson disease
Epidemiology
Sites
  • Liver, cornea, kidneys and brain
Pathophysiology
Etiology
  • Oxidative damage to hepatocytes due to toxic accumulation of copper
Diagrams / tables

Images hosted on other servers:

Normal copper and iron metabolism

Impaired copper and iron metabolism

Clinical features
Diagnosis
  • Suspect Wilson disease in children and adults with unexplained liver enzyme elevations
  • Diagnosis may be challenging (Hepatology 2008;47:2089)
  • Low serum ceruloplasmin levels (< 50 mg/L)
  • Increased 24 urine copper (> 100 µg in symptomatic, > 40 µg in others)
  • Liver copper concentration (dry weight) > 250 µg/g
  • Kayser-Fleischer (KF) rings in cornea (slit lamp examination); absence of Kayser-Fleischer ring does not exclude Wilson
  • Mutational analysis for ATP7B (difficult since most patients are compound heterozygotes): gene alterations can be found in Wilson disease
Laboratory
  • Elevations of alanine transaminase (ALT) and aspartate transaminase (AST)
  • Low serum alkaline phosphatase (ALP)
  • Serum ceruloplasmin levels < 50 mg/L
  • Increased 24 urine copper > 100 µg in symptomatic, > 40 µg in others
  • Liver copper concentration (dry weight) > 250 µg/g
  • Positive antismooth muscle or antinuclear antibodies with elevated gamma globulin levels in some patients (may mimic autoimmune hepatitis)
  • Reference: Hepatology 2008;47:2089
Radiology description
  • No pathognomonic findings
  • Attenuation abnormalities may be seen diffusely in the liver on CT (hyperdense liver can be seen); however, this is finding is variable and can be due to other causes of metal deposition in the liver, such as iron overload due to hemochromatosis (Eur J Radiol 2007;61:25)
  • Parenchymal heterogeneity on ultrasound has also been reported though nonspecific (Eur J Radiol 2007;61:25)
  • Morphologic changes of cirrhosis including regenerative nodules and surface contour nodularity may be seen and are typically nonspecific as to underlying cause; however, MRI findings of hyperintense nodules on T1 weighted imaging and hypointense nodules on T2 weighted imaging in the setting of Wilson disease have been reported (Radiographics 2010;30:e38)
Case reports
Treatment
  • D penicillamine and trientine: oral chelating agents
  • Zinc salts: inhibit absorption of copper
  • Liver transplantation: phenotype correction reserved for patients with cirrhosis or fulminant liver failure
  • Other experimental treatments (Transl Gastroenterol Hepatol 2021;6:21)
Gross description
  • No pathognomonic gross characteristics of Wilson disease
  • Gross findings vary based on the disease histology and phase
  • Cases with fulminant hepatitis with parenchymal necrosis will have a small shrunken liver
  • Cases with chronic long term disease who developed cirrhosis will exhibit features of cirrhosis on gross examination
Gross images

Images hosted on other servers:

Liver with cirrhosis

Liver with necrosis and parenchymal collapse

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by ILKe Nalbantoglu, M.D. and Zafar Ali, M.D. (Case #388)
 

Normal architecture, patchy steatosis

Steatosis and glycogenated nuclei

Acute hepatitis


Fulminant hepatitis

Hepatitis

Cirrhosis

Copper stain (rhodamine)

Positive stains
Negative stains
  • Negative copper stain does not exclude Wilson disease
Electron microscopy description
Molecular / cytogenetics description
  • ATP7B mutation (more than 300 mutations)
  • Mutational analysis can be difficult since most patients are compound heterozygotes
Sample pathology report
  • Liver, needle core biopsy:
    • Mild steatosis with inflammation
    • Focal portal fibrosis (see comment)
    • Comment: Sections of the liver show a preserved architecture. Steatosis comprising approximately 10% of the liver parenchyma is seen in a nonzonal distribution. Hepatocyte ballooning and Mallory-Denk bodies are not appreciated. Glycogenated nuclei are seen. Lipofuscin pigment deposition in zone 3 hepatocytes is identified. Lobules show mild lobular inflammation with rare acidophil bodies. Portal tracts have minimal inflammation and preserved bile ducts. Reticulin stain confirms preserved architecture. Trichrome stain shows focal portal fibrosis. PASD is negative for diastase resistant globules within hepatocytes. Iron stain is negative.
    • The histologic findings are not diagnostic of a specific entity. The findings of steatosis and inflammation may be in keeping with fatty liver disease in the proper clinical setting. However, other etiologies, including drugs and metabolic diseases (such as Wilson disease), are in the differential diagnosis. Clinical correlation is recommended.
Differential diagnosis
  • Since the histologic features can mimic any liver injury, clinical suspicion is the key for diagnosis of Wilson disease
  • Some of the differential diagnoses include but are not limited to:
    • Fatty liver disease:
      • No definitive distinguishing features
      • Hepatocyte ballooning, Mallory-Denk bodies in pericentral hepatocytes and zone 3 pericellular fibrosis are features of fatty liver disease
    • Autoimmune hepatitis:
      • No definitive distinguishing features
    • Chronic hepatitis:
      • No definitive distinguishing features
      • Wilson disease should be suspected in any patient with unexplained liver enzyme elevations
    • Drug induced hepatitis:
      • No definitive distinguishing features
      • Clinical history of medication exposure can help
Board review style question #1
Which of the following is a feature of Wilson disease?

  1. ATP7B mutations are found in these patients
  2. Autosomal dominant
  3. Disease affects liver only
  4. Patients will have high serum ceruloplasmin
  5. Patients will have low hepatic copper
Board review style answer #1
A. ATP7B mutations are found in these patients

Comment Here

Reference: Wilson disease
Board review style question #2


Which of the following is true regarding the morphologic findings in Wilson disease?

  1. Chronic hepatitis is almost never seen in these patients
  2. Electron microscopy findings are pathognomonic for Wilson disease
  3. Histologic and serologic findings can mimic autoimmune hepatitis
  4. Positive copper stain confirms the diagnosis of Wilson disease
  5. Steatosis is rarely seen in these patients
Board review style answer #2
C. Histologic and serologic findings can mimic autoimmune hepatitis

Comment Here

Reference: Wilson disease
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