title: Fulminant hepatitis following crizotinib administration for ALK-positive non-small-cell lung carcinoma.
abstract: We herein report a case of fatal fulminant hepatitis secondary to crizotinib administration. The patient was 54-year-old female with a history of Hepatitis C infection (not current), dermatomyositis and steroid-induced diabetes mellitus. She was diagnosed with advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement. We began 400 mg of crizotinib as first-line therapy. No adverse effects were seen until Day 16. On Day 29, she was admitted to hospital with elevated liver enzymes (aspartate aminotransferase 3236 IU/l, alanine aminotransferase 5201 IU/l) and coagulopathy (prothrombin time <10%), and was diagnosed with crizotinib-induced fulminant hepatitis. We started intensive care, using plasma exchange, continuous hemodiafiltration and high-dose steroid therapy. Unfortunately, she did not respond to therapies, and died on Day 36. The mechanism and risk factors of crizotinib-induced hepatotoxicity are uncertain. Physicians should be aware of possible adverse effects of crizotinib. A systemic survey is imperative to identify possible risk factors of crizotinib-related hepatotoxicity.
authors: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe.
authors: Yuki
authors: Y
authors: Sato
authors: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe daichianzen@yahoo.co.jp.
authors: Daichi
authors: D
authors: Fujimoto
authors: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe.
authors: Yumi
authors: Y
authors: Shibata
authors: Department of Anesthesiology, Kobe City Medical Center General Hospital, Kobe.
authors: Ryutaro
authors: R
authors: Seo
authors: Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe.
authors: Yoshiki
authors: Y
authors: Suginoshita
authors: Department of Pathology, Kobe City Medical Center General Hospital, Kobe, Japan.
authors: Yukihiro
authors: Y
authors: Imai
authors: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe.
authors: Keisuke
authors: K
authors: Tomii
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000628:therapy; D000077547:Crizotinib; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic lymphoma kinase; crizotinib; drug induced liver toxicity; fulminant hepatitis; tyrosine kinase inhibitor