Transcript Case - University of Wisconsin–Madison

Acute Hepatitis in a 19 Year Old
Weightlifter on Dietary Supplements
Ann Sheehy Reed, M.D., M.S.
May 30, 2007
Case History
• 19 year old previously healthy male
• 8 days of fatigue, malaise, painless jaundice
• No travel history, high-risk sexual activity,
tattoos, IVDU, transfusions, ill contacts, or
family history of liver disease
• No acetaminophen or alcohol use
• + use of nutritional supplements containing
creatine and androstendione for two months
prior to admission
Exam
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Vital signs normal
Alert and oriented in NAD
Scleral icterus, jaundice
Normal heart, lung, and abdominal exam
Subtle confusion (only apparent to family)
No asterixis
Admission Laboratory Tests
Total bilirubin
Ammonia
AST
ALT
Alkaline Phosphatase
INR
PTT
CBC and electrolytes
40.8
162
1,129
1,512
225
1.9
43.0
normal
Acute Hepatitis
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Acetaminophen and ethanol negative
Hepatitis A, B and C negative
HIV, EBV, CMV negative
Ceruloplasmin 22 mg/dl (18-55)
Serum total copper 94 mcg/dl (70-140)
Kayser-Fleischer rings absent
Hepatic imaging: echogenic liver, normal
blood flow, no masses
Further Studies
• Liver Biopsy:
– Cirrhosis with areas of
recent hepatocellular
necrosis
– Marked increase in
copper staining
– 199mcg/g dry hepatic
weight (10-35)
Apoptotic
hepatocyte
• 24 hour urine copper:
– 408 mcg/L (2-30)
fibrosis
Dietary Supplements
• Revealed copper
concentrations of 0.42
and 0.70 mcg/g
• Neither supplement
listed copper as an
ingredient
Diagnosis: Wilson’s Disease
(Hepatolenticular Degeneration)
• Discovered in 1912 by Kinnear Wilson
• Prevalence of 30 cases per million
• Autosomal recessive disease located on
chromosome 13 involving P-Type ATPase
(ATP7B), gene discovered 1993
• Disease causes impaired copper
incorporation into ceruloplasmin and
excretion into bile
Copper Metabolism
• RDA copper: 1.5 mg/day (average US
consumption 0.96 mg/day)
• Essential trace element
• Catalytic activity of essential enzymes
– Involved in collagen cross-linkage, myelin
production, skin, hair, and eye pigmentation
• Copper excretion
– 40% not absorbed
– 60% absorbed: bile, urine
Copper Homeostasis and
the Effect of Wilson’s Disease
X
Presentation
• Age: 5-45, almost all before age 30
– Case report of 3 year old and 62 year old
• Liver 33%:
– Acute hepatitis and/or fulminant hepatic failure
– Chronic hepatitis/cirrhosis
• Neurologic 33%:
– Parkinsonism, tremor, dysarthria
– May progress to total bedridden state
• Psychiatric 33%:
– Depression, personality changes, psychosis,
decline in school/work performance
Diagnosis: A Challenge
• Serum copper: not helpful
• Ceruloplasmin: acute phase reactant
• Kayser-Fleischer rings:
– 50% with hepatic presentation, 90% neuro
• 24 hour urine copper
– Virtually diagnostic if greater than 100 mcg/24 hours,
must have copper free collection container
• Liver biopsy: best test
– Greater than 200-250 mcg/g dry hepatic weight
– Variability if cirrhosis/fibrosis
• Genetics:
– >100 mutations, pts typically heterozygotes
– Limited to siblings
Treatment
Rx
Method
Comments
Dimercaprol
(BAL)
Increase urinary excretion
•First Rx
•Injections
•Not used anymore
Penicillamine
Chelator: reduce protein
affinity for copper, copper
binds penicillamine,
excreted in urine
•Pyridoxine deficiency
•Rash, N/V, heme abnl,
autoimmune disease
•May initially worsen
neuro disease, 10-50%
Triene (Trientine)
Chelator
•Decreases HDL
•Few side effects
•May be as effective,
less well studied
Zinc
Decreases intestinal
copper absorption
•Slow onset
•Typically maintenance
Our Patient: 1Year Follow-up and
Prognosis
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Asymptomatic, teaching martial arts
On penicillamine 250 mg QID, pyridoxine 25 mg qd
Bilirubin 2.1, AST/ALT 51/74
Repeat liver biopsy:
– Significant reduction in amount of stainable
copper, mild to moderate nonspecific inflammation
• May experience normal life expectancy and quality of
life with early diagnosis and treatment with
penicillamine
Summary
• Wilson disease is a rare and somewhat
complicated diagnosis to make
• Needs to be considered in young patients with
acute or chronic hepatitis
• 24 hour urine copper and liver biopsy
– Serum tests not definitive
• Early diagnosis can prevent neuro/psych
complications and could permit normal life
expectancy
• Investigate supplement use
References
• www. fda. gov
• Brewer GJ, et al. Wilson Disease. Medicine
(Baltimore) 1992; 71 (3), 139-164.
• El-Youssef M. Wilson Disease. Mayo Clin Proc
2003; 78, 1126-1136.
• Roberts E and Schilsky M. A Practice Guideline
on Wilson Disease. Gastroenterology 2003; 14751491.