Asparaginase-induced hepatotoxicity: rapid development of cholestasis and hepatic steatosis.

Hepatology International
Natasha KamalDrug-Induced Liver Injury Network

Abstract

L-Asparaginase is a bacterial enzyme used in the treatment of acute lymphoblastic leukemia. In the ongoing U.S. Drug-Induced Liver Injury Network (DILIN) prospective study, standard and pegylated asparaginase were the most frequent cause of liver injury with jaundice among anti-cancer agents (8 of 40: 20%). The unique features of this hepatotoxicity are described. Eight cases from 5 DILIN centers were reviewed for clinical course, laboratory values, imaging, and histopathology. Seven females, aged 29-59 years, and one 8-year-old boy, all with leukemia, developed jaundice within 9-21 days (median 15 days) of starting asparaginase or pegaspargase, during the first (n = 6) or second (n = 2) cycle. Prominent symptoms were jaundice (n = 8), fatigue (6), abdominal pain (6) but rarely pruritus (1). Initial median ALT level was 284 U/L (range 83-1076), Alk P 159 U/L (64-452), and bilirubin 4.4 mg/dL (3.7-8.4). Bilirubin levels rose thereafter in all patients to median peak of 17.5 mg/dL (11.7-25.7), INR rose to 1.1-1.7 and serum albumin fell to 1.5-2.6 g/dL. Hepatic imaging revealed fatty liver in all patients. Liver biopsy showed steatosis but minimal hepatocyte necrosis. One patient restarted on pegaspargase re-developed less severe ...Continue Reading

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Citations

May 13, 2021·Current Hematologic Malignancy Reports·David O RileyFiras El Chaer
May 25, 2021·Frontiers in Pharmacology·Pragyan AcharyaRalf Weiskirchen
Oct 7, 2021·Preparative Biochemistry & Biotechnology·Hesham SaeedNefertiti El-Nikhely

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