title: Vemurafenib-induced granulomatous hepatitis.
abstract: Vemurafenib (Zelboraf; Genentech, CA) is a highly effective oral chemotherapy agent for patients with metastatic melanoma who carry the BRAF V600E mutation. Side effects of this protein kinase inhibitor (PKI) include arthralgia, rash, and fatigue, which are reported in up to one third of treated patients. Mild abnormalities in liver biochemistries were reported with vemurafenib use in 30% of subjects, 11% developed severe laboratory abnormalities, and acute liver failure has been reported (Table ). Herein, a case of severe vemurafenib-induced granulomatous hepatitis leading to chronic cholestasis is reported along with a review of the hepatotoxicity of other PKIs.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Spengler
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006099:Granuloma / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007150:Immunohistochemistry; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D010091:Oximes / Q000008:administration & dosage; D019233:Retreatment; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C561627:dabrafenib