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

• 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 40.8Ammonia 162AST 1,129ALT 1,512Alkaline Phosphatase 225INR 1.9PTT 43.0CBC and electrolytes normal

Acute Hepatitis

• 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)

• 24 hour urine copper: – 408 mcg/L (2-30)

fibrosis

Apoptotic hepatocyte

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

TreatmentRx

Dimercaprol (BAL)

Penicillamine

Triene (Trientine)

Zinc

Method

Increase urinary excretion

Chelator: reduce protein affinity for copper, copper binds penicillamine, excreted in urine

Chelator

Decreases intestinal copper absorption

Comments

•First Rx•Injections•Not used anymore

•Pyridoxine deficiency•Rash, N/V, heme abnl, autoimmune disease

•May initially worsen neuro disease, 10-50%

•Decreases HDL•Few side effects•May be as effective, less well studied

•Slow onset•Typically maintenance

Our Patient: 1Year Follow-up and Prognosis

• 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; 1475-1491.