L-Asparaginase-induced fulminating liver dysfunction

Abstract

A 40-year-old woman with no past medical history was diagnosed with B lymphoblastic leukemia (ALL), and received induction chemotherapy with L-asparaginase (Lasp), cyclophosphamide, doxorubicin, vincristine, and prednisolone. On day 20 of treatment, 2 days after the fifth administration of L-asp at a dose of 3000 KU/m/day, laboratory tests showed deranged liver function with elevated total bilirubin (2.2 mg/dL, normal 0.3–1.0), AST (70 U/L, normal 8–34), and ALT (43 U/L, normal 13–31). A computed tomography (CT) scan on day 26 revealed severely diffuse low-density of the liver (Fig. 1b), which was not observed at the onset of ALL (Fig. 1a). Furthermore, total bilirubin, AST, and ALT increased to 4.1 mg/ dL, 640 U/L, and 693 U/L, respectively. Because L-asp was suspected to have induced the fulminating liver dysfunction, the next dose of L-asp was discontinued, and ursodeoxycholic acid was administered for liver protection. While CT on day 40 showed similar results (Fig. 1c), on day 100 liver density had nearly recovered to its pre-chemotherapy state, followed by normalization of laboratory findings (Fig. 1d). Thereafter, she achieved and maintained a complete remission after the post-remission therapy, which included allogeneic hematopoietic stem cell transplantation. Although liver injury due to L-asp seems to be a wellknown adverse effect, impressive CT images such as in this case, possibly due to severe fatty liver, have rarely been reported. The mechanism of liver steatosis remains to be elucidated, but asparaginase may cause abnormalities in lipid metabolism by inhibiting protein synthesis. Such liver dysfunction may occasionally develop into fatal liver failure. This case suggests the importance of evaluating periodic CT scans for liver dysfunction after treatment with L-asp. CT images may be useful not only for early