Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors

Abstract

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia, Philadelphia-positive acute lymphoblastic leukemia, and advanced gastrointestinal stromal tumors. Several cases of hepatotoxicity, including fatal liver failure, have been reported with the long-term use of imatinib mesylate. Generally hepatotoxicity resolves after discontinuation of imatinib. Despite discontinuation of imatinib, hepatotoxicity can be progressive. Steroid may be useful in these patients and should be started early. We report a 53-year-old woman with advanced gastrointestinal stromal tumors who developed hepatotoxicity while receiving imatinib and subsequently acute liver failure. Ten weeks after commencing imatinib treatment, hepatotoxicity was determined. Imatinib was immediately ceased. Subsequently, a week later hepatic encephalopathy, jaundice, and coagulopathy occurred. Prednisolone was commenced. Liver biopsy was performed five weeks after the determining of hepatotoxicity. Biopsy showed sinusoidal congestion, necrosis of hepatocytes, inflammation, and hepatocyte drop out around the hepatic venule consistent with drug toxicity. Her liver function tests normalized with a nine-week prednisolone treatment. The patient was discharged. Her liver enzymes remained in normal range following visits. In cases of imatinib-induced acute hepatitis, the administration of prednisolone may be useful in the resolution of the acute episode and allow the reintroduction of a drug without risking recurrence of hepatitis.

Hepatotoxicity of targeted therapy for cancer

“…[14,17] In patients with severely abnormal liver function tests associated with lapatinib, imatinib and erlotinib, liver biopsies mostly showed diffuse portal-to-portal, portal-tocentral and centrilobular necrosis, inflammation and interface hepatitis. [64,76,77,78] Yet, cholestatic injury has also been reported with imatinib. [33,79] Imatinib-induced hepatotoxicity has also been shown progress to cirrhosis with portal hypertension, months after LFTs had normalised.…”

Hépatotoxicité tardive à l’imatinib chez une patiente de 44 ans

“…Ainsi, quatre des cinq patients de l'équipe de Ferrero et al, de même que le patient de Tonyali et al, ont eu une nette amélioration des taux de transaminases sous corticothérapie [13,14]. La réintroduc-tion de l'imatinib, associée à un corticoïde, n'a pas été suivie d'une récidive parmi les cas de Ferrero et al, ouvrant de nouvelles perspectives thérapeutiques [13].…”

Formation of reactive metabolites and management of tyrosine kinase inhibitor-induced hepatotoxicity: a literature review

“…Furthermore, the possible risk of increased RM formation through enzyme induction would have to be carefully considered. A previous study conducted by our group demonstrated an increase in risk of hepatotoxicity with the concomitant use of lapatinib and dexamethasone [53], which [59] IMA Treatment Prednisolone 100 mg/day 3 days [44] IMA Treatment Prednisolone 0.8 mg/kg/day 2 months [56] IMA Prevention Prednisolone 25 mg/day 5 months [45] IMA Prevention Prednisolone 25 mg/day 2 months [48] IMA Prevention Prednisolone 20 mg/day N.A. [49] IMA Prevention Prednisolone 50 mg/day N.A [50] IMA Treatment and prevention Prednisolone 1 mg/kg/day 6 months [46] IMA Treatment and prevention Prednisolone (T) 1 mg/kg/day (P) 30 mg/day* N.A.…”