Hepatic Copper in Patients Receiving Long-term Total Parenteral Nutrition

Abstract

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.

Dosing and Monitoring of Trace Elements in Long‐Term Home Parenteral Nutrition Patients

“…Copper supplementation should be conservative in patients with cholestasis with regular monitoring of copper status to avoid deficiency. 15,28 The relationship between copper doses and serum copper concentrations was not significant. Because serum copper concentrations were not measured during cholestasis, we could not compare this relationship between patients with and without cholestasis.…”

“…[24][25][26][27] Although copper toxicity has not been reported in PN patients, hepatic copper accumulation may still occur. 28 Autopsies of SBS patients who received copper doses of 1.4 mg/d in their home PN showed copper accumulation in the liver and kidneys, especially in patients who died of liver failure. 3 This raises the concern for potential subclinical copper toxicity that may occur in home PN patients, especially when higher doses are used.…”

“…It is also difficult to predict the duration of copper supplementation that predisposes to copper accumulation, and hepatic copper loading does not correlate with the duration of copper supplementation in home PN. 28 In our study, serum copper concentrations were not measured during cholestasis, and copper doses were likely adjusted empirically based on clinicians' experience whenever serum bilirubin concentrations became elevated. The average frequency of serum copper concentrations measurements was low at 0.39 per year.…”

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

“…Those studies included prophylactic administration of taurosusodeoxycholic acid, 5 cholecystokinin-octapeptide, 6,7 taurine, 8 phenobarbitol 9 and removing copper and manganese from the PN. 10,11 One problem inherent in any prophylactic strategy in the NICU is accurately predicting which neonates are at highest risk for developing the adverse outcome, so that high-risk patients can be eligible for study while low-risk patients can be excluded. Indeed, in the first days of life, when a prophylactic treatment to prevent PNALD might be started, it is not clear how to identify the neonates receiving PN who are at highest risk of developing PNALD.…”

Managing liver dysfunction in parenteral nutrition

“…While it could be argued that since Mn is excreted via the biliary system this increase is simply a consequence of cholestasis rather than a cause, withdrawal of parenteral Mn improves hepatic function in children with high plasma levels (65) . Finally, Cu is also excreted via the biliary route and can accumulate in the liver if there is substantial cholestasis, which may exacerbate hepatic dysfunction (66) .…”