Acute liver injury in the context of immune checkpoint inhibitor-related colitis treated with infliximab

BACKGROUND: Immune checkpoint inhibitors (ICPIs), used to treat different advanced malignancies, are associated with a wide range of immune-related adverse reactions (irAEs) that deserve close monitoring of patients. Gastrointestinal reactions and hepatotoxicity may occur, which warrant careful evaluation to confirm the etiology and attribution to ICPIs as these events could affect future management. CASE PRESENTATION: We describe a case of a patient with prostate adenocarcinoma, treated with dual ICPIs comprised of ipilimumab and nivolumab, who developed elevated liver enzymes in the context of infliximab therapy prescribed to treat gastrointestinal irAE from his ICPIs. The patient’s grade 3 colitis became steroid-refractory, requiring a one-time infusion of infliximab, a biologic agent used commonly in inflammatory bowel disease, as a rescue therapy, to which he responded. The patient subsequently developed liver injury. This presented a diagnostic dilemma involving differential diagnoses of hepatotoxicity due to ICPI or infliximab exposure. A careful review of the clinical history, evaluation of the chronology of events, and exclusion of other causes of acute hepatitis were employed to make the final diagnosis of this event as infliximab-associated hepatotoxicity. CONCLUSION: ICPIs such as CTLA-4 and PD-1 inhibitors have the potential to cause both gastrointestinal reactions and hepatotoxicity. An additional confounding factor in our patient’s case was the exposure to infliximab used to manage an established irAE that developed after the last exposure to ICPIs. The clinical history and data supported infliximab-associated hepatotoxicity, rather than an irAE. With the increasing application of ICPIs for different cancers, in conjunction with potential risks for irAE, the liver profile should be closely monitored during treatment with ICPI as well as with anti-TNF-α agents in this patient population.