Clinical Pearls & Morning Reports
Published January 18, 2017
Wilson’s disease, also known as hepatolenticular degeneration, is an autosomal recessive disease characterized by impaired copper metabolism due to a defective ATPase. Patients with Wilson’s disease may present with chronic liver disease, acute liver failure, hemolysis, and psychiatric or neurologic manifestations. It has been previously noted that viral infection or drug toxicity may serve as a trigger for fulminant Wilson’s disease. A new Review Article explains.
Q: Does acute liver failure in the pediatric population always present with hepatic encephalopathy?
A: Acute liver failure in adults is characterized by a sudden loss of hepatic function without evidence of preexisting liver disease. Criteria for the diagnosis include the presence of coagulopathy (international normalized ratio [INR], >1.5), hepatic encephalopathy, and an illness of less than 24 weeks’ duration. However, in the pediatric population (which can be considered to include patients who are up to 21 years of age), up to 50% of patients who present with acute liver failure do not present with encephalopathy. Modified criteria for the diagnosis of acute liver failure in children include evidence of acute liver injury and severe coagulopathy (INR, >2.0) in the absence of encephalopathy.
Figure 2. (10.1056/NEJMcpc1613467/F2) Causes of Acute Liver Failure in Children and Adults.
Q: What are the rapid diagnostic screening test criteria for Wilson’s disease?
A: Rapid diagnostic criteria for Wilson’s disease can be used in patients who present with acute liver failure. A screen that shows a ratio of alkaline phosphatase (IU per liter) to total bilirubin (mg per deciliter) of lower than 4.0 and then subsequently shows a ratio of aspartate aminotransferase (IU per liter) to alanine aminotransferase (IU per liter) of higher than 2.2 has been described as 100% sensitive and specific for the diagnosis of Wilson’s disease.
A: The pathological diagnosis of Wilson’s disease is generally based on the presence of compatible histomorphologic features and results of staining for copper, including a rhodanine stain. However, staining for copper in tissue is unreliable, since the presence of copper in the cytoplasm of hepatocytes might not be detected on a rhodanine stain. Therefore, in patients with suspected Wilson’s disease, copper quantification performed on either a dedicated core-biopsy specimen or a paraffin-embedded tissue sample is considered to be the best available diagnostic test.
A: In Wilson’s disease, acute liver failure develops in the setting of subclinical chronic liver disease. If liver transplantation is not performed, acute liver failure due to Wilson’s disease is fatal. In this country, the highest priority (United Network for Organ Sharing status 1A) is reserved for patients with liver failure who have a life expectancy of less than 7 days if they do not undergo transplantation. Wilson’s disease is the only cause of acute liver failure that allows a patient with preexisting liver disease to be listed as status 1A. The outcomes associated with liver transplantation for acute liver failure induced by Wilson’s disease are excellent, if transplantation is performed prior to neurologic deterioration.