Hepatic copper in patients receiving long-term total parenteral nutrition.
OBJECTIVE
To assess the possibility of iatrogenic hepatic copper overload in adult patients on long-term total parenteral nutrition (TPN).


BACKGROUND
TPN predisposes to hepatic copper accumulation through disturbances of the enterohepatic bile acid pool, but iatrogenic copper overload through TPN solutions may occur as well.


METHODS
Quantitative hepatic copper and multiple clinical, biochemical, and histopathologic parameters were compared between patients with long-term TPN associated liver disease (n = 28) and patients with drug-induced cholestatic liver disease (n = 10).


RESULTS
Eighty-nine percent of TPN patients and all controls had mildly elevated hepatic tissue copper, but 29% of TPN patients had levels above the diagnostic threshold for Wilson's disease. Quantitative hepatic copper correlated positively with serum aspartate aminotransferase (P = 0.001, r = 0.59), total bilirubin (P < 0.001, r = 0.65), and direct bilirubin (P < 0.001, r = 0.63) in TPN patients, but not in controls. The amount of hepatic copper did not correlate with the duration of TPN (median, 1.9 years; range, 0.3-18.0 years) or serum copper levels. TPN patients with significant cholestasis accumulated more copper than patients with no or only minimal cholestasis (P = 0.002).


CONCLUSIONS
Significant hepatic copper overload in TPN patients occurs through chronic cholestasis in TPN-associated liver disease and is independent from the total duration of TPN. Iatrogenic copper overload through trace elements in TPN solutions does not seem to be a significant factor.
Blaszyk
Hagen
H
Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05401, USA. hagen.blaszyk@vtmednet.org
Wild
Peter J
PJ
Oliveira
Andre
A
Kelly
Darlene G
DG
Burgart
Lawrence J
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D003300:Copper / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007049:Iatrogenic Disease; D007410:Intestinal Diseases / Q000628:therapy; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D013054:Spectrophotometry, Atomic; D013997:Time Factors
D003300:Copper