S5508 An Iron Liver: A Case of Infliximab-Induced Hemochromatosis

Introduction: Hemochromatosis results in iron overload in the liver and can be inherited or acquired, which can lead to hepatic scarring. Infliximab is a TNF-alpha inhibitor used in the treatment of inflammatory bowel disease (IBD). We present a case of infliximab-induced liver injury leading to hemochromatosis, not previously described. Case Description/Methods: A 45-year-old man with a history of Crohn's presented to the hospital with abnormal liver function tests. His medication history included infliximab, rifaximin, propranolol, cetirizine, docusate, mesalamine, gabapentin, budesonide, lamotrigine, and risperidone. A serologic workup revealed elevations in ferritin and iron saturation. An HFE gene analysis and autoimmune workup were unremarkable, and the, magnetic resonance imaging/magnetic resonance cholangiopancreatography was unrevealing for liver/biliary pathology. A hepatitis panel revealed low reactivity for HCV, but hepatitis C virus (HCV) RNA was negative. He denied alcohol, illicit drug, or acetaminophen use. His liver biopsy was significant for acute-on-chronic hepatitis with areas of parenchymal collapse and bridging necrosis, favoring drug-induced liver injury (DILI) secondary to infliximab. Extensive iron deposition was noted in hepatocytes, bile ducts, and Kupffer cells, with no prior transfusions. The initial hepatic panel revealed the following results: Alb 2.3, alkaline phosphatase 133, TBili 2.6, Conjugated Bili 1, aspartate aminotransferase 119, alanine aminotransferase 116, gamma-glutamyl transferase P 110, LDH 433. Due to low levels of the drug, dose frequency was increased from bi-monthly to monthly. After DILI was recognized, he was switched to vedolizumab. Discussion: Previous case reports have shown DILI associated with infliximab therapy, but no literature described iron-related DILI with infliximab. This patient had no history of previous iron-related disorders. Biopsy confirmed iron overload in hepatocytes, consistent with elevations in ferritin and iron parameters. The timing of dose escalation coincided with the timing of liver injury, implying that infliximab may alter iron metabolism. Infliximab may promote either an increased storage or decreased clearance of iron. Once infliximab was stopped, liver enzymes and iron studies took years to normalize, and fibrosis scores remained elevated. Given that iron deposition can cause liver fibrosis, this supports iron-related DILI as a result of infliximab therapy. This case shows a subset of DILI to infliximab had not been previously documented. It broadens differential diagnoses when treating IBD patients with infliximab, and raises new benefit/risk discussions of infliximab therapy.