2297 Tyrosine Kinase Inhibitor-Induced Hepatotoxicity: A Case Series

Abstract

INTRODUCTION: Tyrosine kinase inhibitor (TKI) is indicated for the treatment of multiple cancers. Known side effects include vomiting, myalgia, skin rash, bone marrow suppression and mild hepatotoxicity. We report two cases of TKI-mediated hepatotoxicity with variable outcomes in patients with no prior history of chronic liver disease (CLD). CASE DESCRIPTION/METHODS: CASE 1: A 66-year-old Caucasian woman developed maculopapular rash, fatigue, low-grade fevers, neutropenia and significant transaminemia (hepatocellular injury) a month after initiation of Imatinib for GIST (Table 1). Workup for alternative explanation of abnormal liver function test (LFT) including autoimmune markers were unremarkable and TKI was discontinued due to presumed hepatotoxicity. A liver biopsy was performed showing features of drug-induced liver injury (DILI) with patchy perivenular, focal bridging, necrosis, mild cholestasis, portal and mild periportal fibrosis. Her LFTs worsened despite a trial of prednisone. Six months later, a repeat liver biopsy and imaging showed cirrhotic changes (Figure 1). CASE 2: A 85-year-old Hispanic woman with metastatic renal cell carcinoma was started on TKI complained of fatigue and new onset jaundice (Table 2). After a negative work-up for her abnormal LFTs, a liver biopsy was performed which showed changes consistent with drug-related hepatitis (Figure 2). Hence, systemic steroids were started with a gradual normalization of LFTs without any cirrhotic changes on imaging. DISCUSSION: Hepatotoxicity is a known side effect of Imatinib generally manifesting as hepatocellular injury in as many as 2.7% of patients. Cases have ranged from mild elevation in transaminases to progressive irreversible cirrhosis, which has resulted in death. Histologic features of TKI-induced hepatotoxicity include inflammation, fatty degeneration, and liver necrosis. Most hepatotoxicity improves after discontinuation of the drug with limited date on use of systemic steroids. However, cirrhosis due to TKI in-spite of drug discontinuation and treatment with prednisone is not common. Since there are no guidelines on treatment, oral steroids should be considered, apart from periodic monitoring of LFTs for patients on TKI. Infrequently, orthotopic liver transplantation in patients with decompensated cirrhosis is required. We present two cases of TKI mediated hepatocellular injury with different overall outcomes in spite of similar treatment protocol suggests different mechanisms for DILI.