Present interpretation of the role of copper in Indian childhood cirrhosis.

A common killer disease of the past, Indian childhood cirrhosis (ICC), which became preventable and treatable in the early 1990s, is now rare. ICC must be clearly distinguished in Indian children from other chronic liver disorders including Wilson disease. Grossly increased hepatic, urinary, and serum copper concentrations are characteristic of ICC. These increased concentrations are easily demonstrated histologically with orcein-rhodanine staining. Environmental ingestion of copper appears to be the most plausible explanation for ICC, as shown by feeding histories, the prevention of ICC is siblings and in the Pune district by a change in feeding vessels, and the dramatic reduction in incidence of ICC throughout India. The nature and role of a second factor in the causation of ICC remains unclear, although an inherited defect in copper metabolism is strongly suspected. ICC, however, does not appear to be a straightforward early onset of Wilson disease because ceruloplasmin is consistently normal and clinical and histologic recovery is maintained in the long term despite withdrawal of D-penicillamine therapy. Descriptions of an ICC-like illness in the West suggest that different mechanisms (environmental, genetic, or both) can lead to the same end-stage liver disease: copper-associated childhood cirrhosis. ICC probably represents a specific form of copper-associated childhood cirrhosis that requires high environmental copper ingestion for its full expression.