GOALS: 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. STUDY: 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.
GOALS: 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. STUDY: 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.