Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed. (HEPATOLOGY 1990;11:646-661.)
Cocaine, one of the earliest drugs used by man, is popular because of its tremendous stimulant and euphoriant effects. The most recent surge in usage in the past 10 to 15 yr relates to a greater awareness of the drug and its effects, its greater availability and lower relative cost. Consequently, more reports are seen in the literature concerning cocaine, its toxic effects and organ-system injuries, most notably those affecting the central nervous system (seizures, psychoses, hallucinations, strokes), the cardiac system (dysrhythmias, myocardial infarction) and the neuromuscular system (rhabdomyolysis) (1-3).
Cocaine-related liver cell injury was first described in studies of animals by Ehrlich in 1890 (4); extensive experimental studies have been published since interest