S2408 Sunitinib-Induced Acute Liver Failure: A Case Presentation

Abstract

INTRODUCTION: Drug-induced liver injury is an uncommon but a life-threatening entity. Sunitinib, a tyrosine kinase inhibitor (TKI), is used for advanced and imatinib-refractory gastrointestinal stromal tumors. It causes a transient elevation of liver enzymes in about 39% of patients while grade 3 and 4 hepatotoxicities in 3 % of patients. The incidence of fatal acute liver failure is rare. The incidence of acute cardiomyopathy is seen in 10% of patients. We present a case of fatal acute liver failure and cardiomyopathy within two weeks of sunitinib therapy initiation for advanced pancreatic neuroendocrine carcinoma. CASE DESCRIPTION/METHODS: A 64-year-old male with stage IV high grade pancreatic neuroendocrine carcinoma with metastasis to the liver, spleen, and left adrenal gland, presented with right upper quadrant abdominal pain, nausea, and lethargy. The patient was started on Sunitinib, a month prior to presentation. It was discontinued two weeks before admission due to severe fatigue, decreased oral intake, and dehydration. Physical exam was positive for jaundice, disorientation to time, place, and person and asterixis. The trend of liver function tests during the course of hospitalization is presented in Table 1. The workup to determine other causes of acute liver failure was unremarkable. The patient was started on N-acetylcysteine protocol for acute liver failure and lactulose and rifaximin for suspected hepatic encephalopathy. The patient was not a candidate for a transplant due to stage IV cancer. Transthoracic echocardiography showed new-onset severe acute cardiomyopathy with an ejection fraction of 20–25%. The patient's mental status did not improve despite 3–4 bowel movements per day. Despite aggressive supportive care, his liver failure was irreversible and the patient passed away on day 5 of hospitalization. DISCUSSION: Sunitinib causes time and concentration-dependent cellular injury. The pattern of liver injury is typically hepatocellular. Definitive management of organ dysfunction includes withholding of sunitinib along with supportive care. This case emphasizes that overt liver failure and systolic cardiac dysfunction are infrequent but possibly fatal complications of Sunitinib therapy. We recommend periodic monitoring of baseline liver function and cardiac function status for patients on Sunitinib therapy, especially within the first year of treatment.Table 1.: The trend of liver function tests during the course of hospitalization.