Liver structure and function in patients poisoned with chlordecone (kepone)

Abstract

A group of 32 men who worked in a factory that manufactured the organochlorine pesticide, chlordecone, had high levels of this chemical in samples of blood, adipose tissue and liver, and clinical manifestations of chlordecone toxicity (or both). The liver was enlarged in 20 patients and splenomegaly was present in 10. Blood tests of liver functions generally were normal as was sulfobromophthalein clearance from plasma. Examination of a typical patient's liver biopsy by light and electron microscopy revealed such nonspecific findings as increased lipofuscin, minimal fatty metamorphosis, hyperglycogenation of nuclei, mild portal or lobular inflammatory changes, and paracrystalline mitochondrial inclusions. Most notable was the marked proliferation of smooth endoplasmic reticulum, which suggested that chlordecone may induce drug metabolizing enzymes in human liver. This was confirmed by demonstrating that the patients' urinary excretion of glucaric acid was increased and clearance of antipyrine from blood was accelerated when compared to values in healthy controls. An important finding was that plasma γ-glutamyl transpeptidase activity was normal in these patients, illustrating that, as a marker of induction of hepatic drug metabolism, this test may give false-negative results. Two to three years after the patients' exposure to chlordecone had ceased, the pesticide had disappeared from the tissues, the liver and spleen had returned to normal size, hepatic ultrastructural changes had resolved, and urinary excretion of glucaric acid had declined to the normal range. We conclude that the observable hepatic responses to the presence of chlordecone largely represent adaptive changes that are reversible upon elimination of this environmental chemical from the body.