2417 PEG-Asparaginase (PEG-ASP) Induced Liver Injury: Case Report and Systematic Review of the Literature

Abstract

INTRODUCTION: Drug induced liver injury (DILI) is the most common cause of acute liver failure (ALF) in the USA. L-asparaginase (L-ASP) and its pegylated form (PEG-ASP) are antineoplastic agents used in acute leukemias. Here we present a case of severe DILI secondary to PEG-ASP and a systematic review of published cases. CASE DESCRIPTION/METHODS: Methods: PubMed search detected 343 abstracts related to ASP, of which 18 were relevant to our case. We used descriptive statistics to compare the published experience with our patient. Case: A 45 yo female with acute lymphoblastic leukemia (ALL) was admitted with a cholestatic liver injury and jaundice 14 days after starting PEG-ASP. She had normal liver enzymes prior to onset of treatment. Tests for viral and autoimmune hepatitis were unremarkable. Diagnostic ultrasound suggested only a fatty liver parenchyma. Liver biopsy revealed severe steatosis and mild cholestasis without fibrosis. Naranjo scale was 6 consistent with probable adverse drug reaction. PEG-ASP was stopped, steroids and L-carnitine infusion were started, however DILI continued to worsen. At their peak Total/direct bilirubin were 21/17 mg/dL, ALP 1,504 U/L, GGT 2,329 U/L and AST/ALT 153/50 U/L. Patient never developed ALF. Liver enzyme panel normalized over the next 8 weeks. Results: In our review of 18 reported cases, most were females (72%), adults (72%), with 32% being adults <50 years. The patterns of liver enzyme abnormality were cholestatic (26%), hepatocellular (21%), or mixed (21%) (unknown in 32%). Median time from starting ASP to DILI was 17 days. When biopsy was performed (11 patients) macrovesicular steatosis was uniformly present. Overall 6 patients died (one died of ALF) and 12 recovered with normalization of liver enzymes over the course of 2-26 weeks. DISCUSSION: Our patient is a classic case of DILI given onset of injury within 2-3 weeks of initiation of treatment, exclusion of alternate etiologies, histopathology showing severe steatosis, and complete normalization of liver enzymes following drug discontinuation. It is important to recognize ASP-DILI as 30% of cases end in ALF or death; nearly all cases will delay important treatment of acute leukemia. L-carnitine was reported as a potential rescue therapy, though its efficacy is uncertain. CONCLUSION: ASP related DILI is marked by severe steatosis and significant liver enzyme abnormalities occurring within weeks of starting treatment and resolving over many weeks after. Prompt recognition and drug discontinuation are imperative.