Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion

Zidovudine is known to be responsible for a mitochondrial myopathy with rag ged-red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis a lone or associated with hepatic abnormalities has also been reported. A sin gle report mentioned the concomitant occurrence of muscular and hepatic dis turbances and lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues were not studied. A 57-year-old man with AIDS, who had b een treated with zidovudine for 3 years, developed fatigue and weight loss. Serum creatine kinase and hepatic enzyme levels were high. Lactic acidosis was present. Liver biopsy showed diffuse macrovacuolar and microvacuolar s teatosis, After withdrawal of zidovudine, creatine kinase, aspartate aminot ransferase, and alanine aminotransferase levels normalised within 5 days, a nd lactacidaemia decreased. Acidosis persisted. The patient became confused and febrile and died 8 days after detection of high blood lactic acid. A m uscle sample obtained at autopsy showed mitochondrial abnormalities with ra gged-red fibres and lipid droplet accumulation. Southern blot analysis show ed depletion of mitochondrial DNA, affecting skeletal muscle and liver tiss ue. No depletion,vas found in myocardium and kidney. This case emphasises t hat zidovudine treatment can induce mitochondrial multisystem disease, as r evealed in our case by myopathy, liver steatosis and lactic acidosis.