Liver copper concentration in Wilson's disease: effect of treatment with 'anti-copper' agents

Serial copper determinations have been made on the livers of 10 patients with Wilson's disease. Two were studied before and eight after the start of treatment in order to assess the effect, if any, on the concentration of the metal. In two patients who were receiving no therapy and in one in whom it had been discontinued, the level of copper rose. In the latter patient, resumption of treatment then resulted in a fall in the level of copper in the liver. A similar fall was seen in seven patients on continuous therapy. In one patient, a very poor complier, there was a tendency for the liver copper concentration to rise over a 5-year period. All three therapies investigated--penicillamine, trientine and tetrathiomolybdate--when taken regularly, appear to be effective in reducing liver copper levels. Sixty-nine single determinations of liver copper have been plotted against time on treatment. This shows that the copper concentration falls rapidly in the first year. Thereafter, there is no linear relationship between the duration of treatment and liver copper. Poor compliers have a higher liver copper concentration than do good compliers. Determinations made from different portions of the liver showed that in only one of 19 examples was there an overlap between the near normal and the abnormal range. The principal mechanism of action of 'anti-copper' agents in Wilson's disease appears to be the mobilization of copper from the tissues, but a secondary detoxifying action may come into play later.