S5734 A Novel Case of Cholestatic Drug-Induced Liver Injury Following Filgrastim Use in a Patient With Neutropenic Fever

Introduction: Drug-induced liver injury (DILI) is a challenging diagnosis due to its variable presentation and extensive work-up. Filgrastim - often used for chemotherapy-induced neutropenia – is generally well tolerated with varying side effects; however, significant hepatotoxicity is rare. This report describes a unique case of DILI following filgrastim use in the inpatient setting. Case Description/Methods: A 70-year-old man with Waldenström’s macroglobulinemia, undergoing monthly chemotherapy with bendamustine and rituximab followed by D1 C2 Ruxience, presented 3 weeks after his fifth infusion, with neutropenic fever. He was febrile to 101°F, HR 140 and BP 95/52. He received 30 cc/kg of Lactated Ringer's, intravenous vancomycin, and cefepime. Additional antibiotics included meropenem, micafungin, and piperacillin-tazobactam. Infectious workup was unremarkable, and antibiotic regimens were stopped. Filgrastim was given on day 2 of admission for 6 days. Initial hepatic panel showed alanine aminotransferase (ALT) 13 U/L, AST 15 U/L, alkaline phosphatase (ALP) 155 U/L, and total bilirubin (TB) 0.6 mg/dL. After one week of filgrastim initiation, ALP was 1000 U/L, ALT 187 U/L, AST 264 U/L, and TB 5.5 mg/dL. Viral and autoimmune serologies, abdominal ultrasound, and MRCP were negative. Three days after stopping filgrastim, labs trended down. Liver biopsy was therefore deferred. Per the Roussell Uclaf Causality Assessment Method (RUCAM) scale, filgrastim was deemed the probable cause for DILI. He was later discharged in stable condition. Discussion: This case underscores filgrastim as a rare but potential cause of DILI. Prior reports are uncommon, with only one reported case, supported by a RUCAM score and similar transaminase pattern.1 Although he received antibiotics, labs remained stable for the first 72 hours before rapidly climbing. Furthermore, he had received those antibiotics in prior stays, without evidence of DILI, and the elevation continued after antibiotic cessation. Chemotherapy was considered a cause; however, he had received the agents prior to admission without noted hepatotoxicity. The patient’s improvement upon filgrastim withdrawal supports its incrimination. Clinicians should recognize DILI in the differential diagnosis of transaminase elevation, even when commonly implicated drugs are not administered. Reference 1. Sharma D, Da BL, Vittal A, Kapuria D, Heller T, Ben Yakov G. Stimulating More Than Just the Granulocytes: Drug-Induced Liver Injury From Filgrastim. ACG Case Rep J. 2019;6(6):e00098.