Copper chelation therapy in intrahepatic cholestasis of childhood

Abstract

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 2 years of copper chelation. Pruritis remained the main symptom and did not improve. Two patients developed D-penicillamine side-effects - one patient after 9 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 7 of 8 patients from 8.6 (2.7-16.2) μmol/g to 3.4 (0.6-16.5) μmol/g (median and range (0.05 <0.05). Histological assessment of serial liver sections revealed increased fibrosis and cholestasis despite reductions in hepatic copper levels during the study. This study showed that D-penicillamine therapy was associated with significant side-effects, while marked clinical, biochemical, or histological improvement did not follow effective copper chelation therapy in intrahepatic cholestasis of childhood.