What are the typical liver function test (LFT) abnormalities in Wilson's disease?

Typical Liver Function Test Abnormalities in Wilson's Disease

Wilson's disease presents with characteristic liver function test abnormalities including modest elevations in serum aminotransferases, low alkaline phosphatase, and an alkaline phosphatase to total bilirubin ratio of less than 2, especially in acute liver failure presentations. 1

Typical LFT Patterns in Wilson's Disease

Aminotransferases

• Relatively modest elevations in serum aminotransferases, typically around 2000 IU/L in acute presentations - significantly lower than seen in other causes of acute liver failure 1
• AST:ALT ratio >2.2 is highly suggestive of Wilson's disease in acute liver failure (sensitivity 94%, specificity 86%) 2
• AST may be higher than ALT, potentially reflecting mitochondrial damage, though this finding is not invariably present 1

Alkaline Phosphatase

• Markedly low serum alkaline phosphatase activity (typically around 40 IU/L) 1
• Low alkaline phosphatase to total bilirubin ratio is a key diagnostic feature 1
• An alkaline phosphatase to total bilirubin ratio <4 has excellent diagnostic value (sensitivity 94%, specificity 96%) 2

Bilirubin

• Elevated bilirubin, often significantly increased in acute presentations 1
• When combined with low alkaline phosphatase, the ratio becomes a powerful diagnostic indicator 1, 2

Clinical Presentations and Associated LFT Patterns

Acute Liver Failure

• Characteristic pattern includes:
  • Modest rises in aminotransferases (typically around 2000 IU/L) 1
  • Low alkaline phosphatase (typically 40 IU/L) 1
  • Coombs-negative hemolytic anemia 1
  • Coagulopathy unresponsive to vitamin K 1
  • Rapid progression to renal failure 1

Chronic Liver Disease

• May present with persistently elevated aminotransferases 1
• Can mimic other chronic liver diseases including:
  • Autoimmune hepatitis - especially in pediatric patients 1
  • Nonalcoholic fatty liver disease - though hepatic steatosis is rarely as severe as in NAFLD 1

Diagnostic Pitfalls and Special Considerations

• Low ceruloplasmin has limited diagnostic value in acute liver failure (sensitivity of only 21-56% depending on measurement method) 2
• Serum copper levels are typically elevated (>200 μg/dL) in acute presentations but may also be elevated in non-Wilson's disease acute liver failure 2
• Hemolysis is common in acute presentations and may be the initial manifestation 1
• Wilson's disease can mimic HELLP syndrome in pregnant patients with undiagnosed disease 3

Diagnostic Algorithm

1. Consider Wilson's disease in any patient with unexplained liver disease, especially those under 40 years 1
2. Calculate the following ratios:
   • Alkaline phosphatase (IU/L) to total bilirubin (mg/dL) ratio <2 strongly suggests Wilson's disease 1
   • AST:ALT ratio >2.2 further supports the diagnosis 2
3. Look for associated findings:
   • Coombs-negative hemolytic anemia 1
   • Low hemoglobin 4
   • Low cholinesterase activity 4
4. Confirm with additional testing:
   • 24-hour urinary copper excretion 1, 4
   • Slit-lamp examination for Kayser-Fleischer rings 1, 4
   • Liver biopsy for hepatic copper concentration when diagnosis remains uncertain 4

The combination of these laboratory abnormalities, particularly the alkaline phosphatase to bilirubin ratio <4 and AST:ALT ratio >2.2, provides excellent diagnostic accuracy with 100% sensitivity and specificity when used together 2.