ROLE OF COPPER IN INDIAN CHILDHOOD CIRRHOSIS

Of the cirrhoses that affect Indian children, Indian childhood cirrhos is (ICC) is a discrete clinical and histologic entity in which large a mounts of copper are deposited in the liver. The evidence linking copp er deposition to increased dietary copper intake in infancy was review ed. Prevention of this feeding pattern prevents ICC, and the disease h as now largely disappeared from many parts of India. Penicillamine, if given before the terminal clinical stage of ICC, reduces mortality fr om 92% to 53%. Long-term survivors show a sequence of histologic resol ution, resulting either in inactive micronodular cirrhosis or in virtu ally normal histologic appearance. Twenty-nine treated ICC patients re examined at 8.8 y of age (range: 6.3-13 y), 5-12 y after diagnosis, we re well and had normal results from liver function tests. Clinical and epidemiologic evidence show that there must be excessive copper inges tion for ICC to develop, but the lack of an animal model, the inconsta nt relation between liver copper concentrations and liver damage, and the rarity of liver disease in adults suggests that other etiologic fa ctors contribute. Two mechanisms are discussed: 1) that copper may be acting in synergy with a hepatotoxin, or 2) that there may be a geneti c predisposition to copper-associated liver damage, as suggested recen tly for Tyrollean childhood cirrhosis. Although ICC is now rare, spora dic cases of an ICC-like disorder in infants continue to occur. There should be a greater awareness among pediatricians of this disease to e nable early diagnosis. Penicillamine should be used early and adverse prognostic factors recognized as indications for early transplantation and unregulated water supplies should not be used to prepare infant f eeds.