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L-Asparaginase is commonly used in combination chemotherapy of both pediatric and adult acute lymphoblastic leukemia. The majority of adverse effects are hypersensitivity reactions, but serious liver injury may also occur. It has been shown that treatment with L-asparaginase can be associated mainly with macrovesicular hepatic steatosis which may be accompanied by alterations in lipid metabolism. So far, the mechanism for liver injury associated with L-asparaginase is not known. We report here an adult patient who developed mixed liver injury and predominantly microvesicular hepatic steatosis while being treated with L-asparaginase for acute lymphoblastic leukemia. The patient developed liver failure and died due to multiorgan failure. Both impaired liver mitochondrial function and alterations in very-low-density lipoprotein metabolism and secretion are discussed as two possible mechanisms explaining the findings observed in this patient.