Types of Liver Disease in Wilson's Disease
Wilson's disease can present with various types of liver disease, ranging from asymptomatic biochemical abnormalities to acute liver failure, chronic hepatitis, and cirrhosis. 1
Spectrum of Liver Disease in Wilson's Disease
Asymptomatic liver disease: Many patients have only biochemical abnormalities without clinical symptoms, detected incidentally during routine testing 1
Chronic hepatitis: Presents with symptoms indistinguishable from other forms of chronic active hepatitis, including jaundice, malaise, and vague abdominal complaints 1
Cirrhosis: Most patients with Wilson's disease have cirrhosis at presentation, which may be compensated or decompensated 1
Acute liver failure: Rapid deterioration with hepatic and renal failure, carrying an almost 95% mortality when untreated; accounts for 6-12% of all patients referred for emergency liver transplantation 1
Clinical Manifestations of Liver Disease
Jaundice, anorexia, and vomiting: Present in 14-44% of patients with liver manifestations of Wilson's disease 1, 2
Ascites and edema: Occur in 14-50% of patients with Wilson's disease presenting with liver symptoms 1, 2
Variceal hemorrhage: Seen in 3-10% of patients as a complication of portal hypertension 1
Hemolysis: Coombs-negative hemolytic anemia occurs in 5-20% of patients, either as the initial symptom or associated with severe liver disease 1
Hepatomegaly/splenomegaly: Present in 15-49% of patients with Wilson's disease 1, 3
Pathophysiology and Progression
Copper accumulation: Wilson's disease is caused by mutations in the ATP7B gene, leading to impaired biliary excretion of copper and its accumulation in the liver 4, 5
Progressive liver damage: Excess copper causes hepatocellular injury, inflammation, necrosis, and eventual cirrhosis 6, 7
Disease progression: Liver disease may precede neurologic manifestations by up to 10 years, with most patients with neurologic symptoms having some degree of liver disease at presentation 1
Special Considerations
Age-related presentation: Liver disease is more common before puberty, while neurologic manifestations tend to predominate in adolescents and young adults 8, 9
Gender differences: Acute liver failure due to Wilson's disease occurs predominantly in young females (female:male ratio 4:1) 1
Treatment response: With proper treatment (chelating agents like penicillamine or trientine, or zinc salts), most patients show symptomatic improvement and normalization of liver function tests within one year 10, 9
Clinical Pitfalls and Diagnostic Challenges
Mimicking other conditions: Acute presentation may be indistinguishable from viral hepatitis or, during pregnancy, may mimic HELLP syndrome 1
Low alkaline phosphatase: A characteristic finding in Wilson's disease with acute liver failure is low alkaline phosphatase with only mildly increased transaminases 1, 2
Delayed diagnosis: Diagnosis may be delayed from 1 week to 8 years after the onset of liver disease, highlighting the importance of considering Wilson's disease in young patients with unexplained liver disease 10, 9