S2660 Imatinib Mesylate (Gleevec)-Induced Acute Liver Failure Successfully Treated With Prednisolone Therapy

Abstract

INTRODUCTION: Imatinib mesylate (Gleevec) is an FDA approved tyrosine-kinase inhibitor for treatment of resected, high-risk and advanced gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia.1-4% of patients on imatinib therapy develop drug-induced liver injury (DILI) with a minority developing acute liver failure, or even death. We report a clinical case of imatinib-induced acute liver failure in a 46-year-old woman with a GIST of the esophagus/mediastinum successfully treated with corticosteroids. CASE DESCRIPTION/METHODS: A 46-year-old woman with stage IIIa posterior mediastinal GIST at the gastroesophageal junction status post-surgical resection with pathology showing 38 mitosis per high power field on adjuvant imatinib therapy since October 2019 presented in December 2019 with emesis, jaundice and encephalopathy. On exam, she had jaundice and grade 3 hepatic encephalopathy with no focal neurological deficit. The liver associated enzymes revealed elevated ALP 165U/I, ALT 694U/I, AST 635U/I and total bilirubin of 3.0 mg/dL. The ammonia level was 65 uMol/L and INR was 2.3 prompting discontinuation of imatinib.During the hospital course, liver enzymes trended up. Serum assessment for viral hepatitis, autoimmune hepatitis, metabolic liver disease and toxicology testing was negative. Liver ultrasound and abdominal MRI were unremarkable. Liver biopsy revealed extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis (Figure 1). A diagnosis of DILI likely secondary to imatinib was made. After initiation of prednisolone, her encephalopathy and jaundice improved. The liver enzymes and total bilirubin also trended down over a 6 week period (Figure 2,3). DISCUSSION: Imatinib therapy can cause serious side effects, such as acute hepatitis and rarely acute liver failure and death. Liver injury is thought onset varies from 6 days to several years after the initiation of treatment. However, in most cases, acute liver injury develops within a period of 2 to 6 months. Hepatotoxicity usually resolves with either dosage reduction or discontinuation of imatinib. The mechanism of imatinib-induced hepatotoxicity is unknown, however, it has been proposed that imatinib causes immune stimulation. In this case, we successfully employed prednisolone as a novel therapy to treat imatinib induced acute liver failure.This supports the notion that liver injury by imatinib is due to systemic inflammation and direct hepatocyte injury.Figure 1.: extensive inflammation of the liver parenchyma consisting primarily of neutrophils and a few lymphocytes with foci of parenchymal loss and bridging necrosis.Figure 2.: Liver enzymes trend after initiation of prednisolone therapy.Figure 3.: Biliribin trend.