S5810 Acute Liver Injury as a Manifestation of Post-COVID Hemophagocytic Lymphohistiocytosis (HLH)

Introduction: Acute liver injury (ALI) is a common yet diagnostically challenging condition with a broad differential, including viral hepatitis, autoimmune disease, ischemia, and drug-induced liver injury (DILI). Rarely, ALI may be the first sign of systemic hyperinflammation such as haemophagocytic lymphohistiocytosis (HLH), a life-threatening syndrome of immune dysregulation. HLH can be triggered by infections (e.g., EBV, CMV), malignancies, or autoimmune disease. Though HLH has been reported during acute COVID-19, post-COVID HLH remains rare. Hepatic involvement may range from mild transaminitis to fulminant liver failure. We report a case of post-COVID HLH presenting primarily with severe acute liver injury. Case Description/Methods: A 57-year-old man with a history of mild COVID-19 infection 3 months prior to his presentation presented with fatigue, fever, confusion, and new-onset jaundice. Physical exam was notable for scleral icterus. Initial laboratory evaluation revealed aspartate aminotransferase 1350 U/L, alanine aminotransferase 1500 U/L, total bilirubin 6.0 mg/dL (direct 4.0 mg/dL), albumin 3.3 g/dL, and international normalized ratio 1.2. Workup for acute liver injury including viral hepatitis panel (A, B, C), EBV, CMV, HIV, HSV, autoimmune markers (ANA, ASMA), acetaminophen/salicylate level, iron studies, and ceruloplasmin, as well as abdominal imaging all were unremarkable except for ferritin (>10,000 ng/mL). There was no reported exposure to medications or supplements known to cause drug-induced liver injury (DILI). Due to persistent fever, cytopenias, and systemic symptoms, along with the significantly high ferritin level, further evaluation for hyperinflammatory syndromes was pursued. The patient met 5 of 9 HLH-2004 diagnostic criteria: fever, splenomegaly (16.7 cm on CT), hyperferritinemia (>10,000 ng/mL), elevated soluble IL-2 receptor levels, and hemophagocytosis on bone marrow biopsy. Multisystem involvement was evident, including myocarditis, and neurologic symptoms. The patient was started on dexamethasone (20 mg BID), leading to rapid clinical and biochemical improvement. He was discharged in stable condition and completed a steroid taper with normalization of liver enzymes and no recurrence. Discussion: This case illustrates post-COVID HLH presenting with acute liver injury—a rare but critical diagnostic consideration. HLH should be included in the differential for unexplained liver injury with systemic signs, especially in the post-COVID setting. Prompt recognition and immunosuppressive therapy are essential for recovery.