What is the most appropriate treatment for a patient with suspected Wilson's disease, presenting with a fine tremor, jaundice, mildly palpable spleen, low serum ceruloplasmin, high 24-hour urine copper, elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase), and impaired liver function (low albumin and high direct and total bilirubin)?

Treatment of Wilson's Disease with Hepatic Presentation

D-penicillamine (Option B) is the most appropriate initial treatment for this patient with symptomatic Wilson's disease presenting with hepatic manifestations, tremor, and confirmed diagnostic findings. 1, 2

Diagnostic Confirmation

This patient has classic Wilson's disease based on:

• Low serum ceruloplasmin - a hallmark finding present in 96% of Wilson's disease patients 3
• Elevated 24-hour urinary copper - typical in symptomatic patients with values >1.6 μmol (>100 μg/day) 1, 4
• Low serum copper (0.8 mmol/L) - consistent with reduced ceruloplasmin-bound copper 1
• Hepatic dysfunction - elevated transaminases (AST 243, ALT 165), low albumin (23 g/L), and hyperbilirubinemia indicating significant liver involvement 1
• Neurological signs - fine tremor of both hands indicating copper accumulation in the basal ganglia 1
• Splenomegaly - suggesting portal hypertension from chronic liver disease 1

Why D-Penicillamine is the Correct Choice

D-penicillamine is a chelating agent that removes excess copper by enhancing urinary excretion, and has been the established first-line treatment with numerous studies attesting to its effectiveness in Wilson's disease. 1, 2

Mechanism and Efficacy

• D-penicillamine chelates copper, forming a soluble complex that is readily excreted in urine 2
• In patients with symptomatic liver disease, recovery of synthetic liver function and improvement in clinical signs typically occur during the first 2-6 months of treatment, with further recovery during the first year 1
• The drug is rapidly absorbed from the gastrointestinal tract and greater than 80% is excreted via the kidneys 1

Dosing Strategy

• Start with incremental doses of 125-250 mg/day, increased by 250 mg increments every 4-7 days to a maximum of 1000-1500 mg/day in 2-4 divided doses 1
• Must be taken on an empty stomach, at least 1 hour before meals or 2 hours after meals, and at least 1 hour apart from any other drug, food, or milk 2
• This gradual escalation enhances tolerability and reduces risk of rapid neurological deterioration 1

Critical Monitoring Requirements

• Weekly CBC, urinalysis, and liver function tests for the first 2-4 weeks, then every 2-4 weeks thereafter 4
• Target urinary copper excretion of 200-500 μg/24 hours (3-8 μmol/24 hr) on treatment 1, 5
• Monitor for proteinuria (>1 g/24 hours requires dose reduction or discontinuation) 2
• Liver function tests every 3 months during the first year 2

Why Other Options Are Incorrect

Corticosteroids (Option A)

• No role in Wilson's disease treatment - this is a copper metabolism disorder, not an autoimmune or inflammatory condition requiring immunosuppression 1, 4
• May only be used if pemphigus develops as a complication of D-penicillamine therapy 2

Desferrioxamine (Option C)

• This is an iron chelator, not a copper chelator - completely inappropriate for Wilson's disease 1
• Has no mechanism of action for removing copper accumulation 2

Ursodeoxycholic Acid (Option D)

• This is a bile acid used for cholestatic liver diseases - has no copper-chelating properties 1
• Does not address the fundamental pathophysiology of copper accumulation in Wilson's disease 4

Important Caveats and Pitfalls

Neurological Worsening

• 10-50% of patients may experience worsening of neurological symptoms during initial D-penicillamine therapy, with 13.8% adversely affected in recent series 1
• This patient already has tremor, so close neurological monitoring is essential during treatment initiation 1
• If severe neurological worsening occurs, consider switching to trientine 4

Side Effects Requiring Vigilance

• Severe side effects requiring discontinuation occur in approximately 30% of patients 1
• Early sensitivity reactions (fever, rash, lymphadenopathy, neutropenia, thrombocytopenia) may occur in first 1-3 weeks 1
• Progressive fall in platelet count or WBC in three successive determinations requires temporary cessation even if values remain within normal range 2
• Proteinuria and hematuria may indicate membranous glomerulopathy progressing to nephrotic syndrome 2

Treatment Adherence

• Once initiated, treatment must be continued daily for life - interruptions for even a few days can cause sensitivity reactions upon reinitiation 2
• Failure to comply leads to significant progression of liver disease and liver failure within 1-12 months 1

Alternative Considerations

While trientine is increasingly preferred over D-penicillamine in children due to lower risk of neurological worsening and fewer severe side effects 4, D-penicillamine remains the established first-line treatment with the most extensive evidence base 1, 2. The 2012 EASL guidelines and FDA labeling support D-penicillamine as the primary chelating agent 1, 2.

For this symptomatic patient with hepatic Wilson's disease, immediate initiation of D-penicillamine with careful dose escalation and intensive monitoring is the standard of care. 1, 2