ArticleHepatology international2019
Asparaginase-induced hepatotoxicity: rapid development of cholestasis and hepatic steatosis.
Article in Hepatology international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Weight Loss During Obesity Provokes Asparaginase-Associated Liver Steatosis and Endoplasmic Reticulum Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Advances in the treatment and prognosis of aggressive NK-cell leukemia: results from the ANKL22 study.Leukemia · 2026Article
- Chronic drug-induced liver injury in a child with acute lymphoblastic leukemia: a case report.BMC pediatrics · 2025Article
- The interaction between IL-17 and gut microbiota contributes to cholestatic liver disease in children.Microbiology (Reading, England) · 2025Article
- Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV.International journal of molecular sciences · 2025Article
- Pegaspargase induced multiple organ failure with acute lymphoblastic leukemia: A case report.World journal of clinical cases · 2025Article
- Induction of Cyp2e1 contributes to asparaginase-induced hepatocyte sensitization to lipotoxicity.Acta pharmaceutica Sinica. B · 2025Article
- Hepatotoxicity associated with anti-neoplastic agents: a pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System database.Frontiers in immunology · 2025Article
- Review
- Exploring the potential of asparagine restriction in solid cancer treatment: recent discoveries, therapeutic implications, and challenges.Medical oncology (Northwood, London, England) · 2024Review
- A Case of L-Asparaginase-Induced Severe Hepatic Steatosis With Decreased Serum Cholinesterase Levels.Cureus · 2023Article
- Asparagine protects pericentral hepatocytes during acute liver injury.The Journal of clinical investigation · 2023Article
- Hepatoprotective effect of nanoniosome loaded Myristica fragrans phenolic compounds in mice-induced hepatotoxicity.Journal of cellular and molecular medicine · 2022Article
- Multiple Asparaginase Infusions Cause Increasingly Severe Acute Hyperammonemia.Medical sciences (Basel, Switzerland) · 2022Article
- Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice.F1000Research · 2022Article
- Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice.Acta pharmaceutica Sinica. B · 2021Article
- L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia.Journal of clinical medicine · 2021Article
- Pegaspargase in Practice: Minimizing Toxicity, Maximizing Benefit.Current hematologic malignancy reports · 2021Review
- Quantifying the difference in risk of adverse events by induction treatment regimen in pediatric acute lymphoblastic leukemia.Leukemia & lymphoma · 2021Article
- Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway.Frontiers in oncology · 2021Article
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundL-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.
methodsEight cases from 5 DILIN centers were reviewed for clinical course, laboratory values, imaging, and histopathology.
resultsSeven 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 injury.
conclusionAsparaginase is a common cause of antineoplastic-induced liver injury with jaundice, typically with short latency, marked steatosis, and prolonged jaundice, which can lead to delays in antileukemic therapy. The cause of injury is likely direct inhibition of hepatic protein synthesis caused by asparagine depletion.
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