Copper chelation therapy in intrahepatic cholestasis of childhood.

Abstract

SUMMARY The effect of copper chelation was studied in a group of children with intrahepatic cholestasis of childhood (IHCC) and increased liver copper levels. Initial therapy was D-penicillamine (10 mg/kg/day), being replaced by triethylenetetramine dihydrochloride (20 mg/kg/day) when side-effects of D-penicillamine occurred. Eight children completed two years of copper chelation. Pruritis remained the main symptom and did not improve. Two patients developed D-penicillamine side-effects -one patient after nine months (marked anorexia, lassitude) and one other patient after 19 months (thrombocytopenia). Two patients died during the study, in one of these normal hepatic copper concentration was achieved. Hepatic copper concentrations decreased in seven of eight patients from 8.6 (2.7-16.2) jumoUg to 3.4 (0.6-16.5) ,umol/g (median and range (OO5<p<0

Copper Toxicity and Lipid Peroxidation in Isolated Rat Hepatocytes: Effect of Vitamin E

“…This potentiating effect of vitamin E deficiency on copper toxicity may have clinical relevance in regard to chronic cholestatic liver diseases, where both secondary hepatic copper overload (37,38) and vitamin E deficiency (39,40) are common. Although it is not certain if copper overload during cholestasis is toxic to the liver (41), we have observed that reversing vitamin E deficiency in children with chronic cholestasis and secondary hepatic copper overload was associated with a decrease of fasting serum bile acid concentrations (42), suggesting that vitamin E repletion lessened hepatic injury and improved hepatic function.…”

The Role of Copper as a Modifier of Lipid Metabolism

“…The under-detection of copper deficiency could be due to limitations of screening using serum or urine samples. Although liver is the main homeostatic organ for copper and has a high copper content, copper levels in serum and urine do not correlate well with a hepatic copper concentration (19), possibly masking deficiency in the liver.…”

Cholestasis Associated with Total Parenteral Nutrition

“…It may be advisable to diminish copper and manganese supplements from the TPN solutions of patients with cholestatic liver disease (120). However, removal of copper by chelation therapy from the livers of children with an excessive copper burden due to cholestatic liver disease (other than Wilson's disease) has not been demonstrated to be of clinical benefit (121). Therefore, the increased retention of these elements during parenteral nutrition is of uncertain toxicity.…”