S5417 Early Liver Abnormalities in Hemophagocytic Lymphohistiocytosis: A Call for Vigilance in Gastroenterology

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome that occurs secondary to uncontrolled immune system activation. Etiology is typically divided into primary (familial) HLH caused by inherited genetic defects and secondary (acquired) HLH triggered by infections, malignancy, or autoimmune processes. We present 2 cases of confirmed HLH to highlight gastrointestinal (GI) involvement in this rare immunologic phenomenon. Case Description/Methods: A 74-year-old man presented with months of fevers and malaise. Two weeks prior, he was hospitalized for sepsis and discharged with oral antibiotics. Initial labs showed aspartate aminotransferase (AST) 134, alanine aminotransferase (ALT) 151, total bilirubin (TB) 1.8, international normalized ratio 1.2 and ferritin 1968. After 2 weeks, AST and ALT decreased, but TB and ferritin continued to rise. With a moderate H score of 128-165 he was started on high-dose steroids. Soluble IL-2 and CD25 labs later confirmed the diagnosis of HLH and the patient was started on etoposide. Despite appropriate treatment, the patient soon required ventilator and pressor support before passing 26 days after presentation. A 34-year-old man presented from oncology clinic due to concern for HLH. Initial labs revealed AST 628, ALT 617, TB 1.5 and ferritin 3256. Three days earlier, he presented to a walk-in clinic with fever. Labs revealed leukopenia and thrombocytopenia. On the first day of admission, the patient's H score was noted to be elevated at 202. He was started on high dose steroids and received an initial dose of etoposide prior to diagnostic confirmation. After initiation of treatment, AST, ALT, TB and ferritin all decreased. Later, diagnostic testing was able to confirm HLH and patient continued treatment managed by oncology. Discussion: Although GI manifestations of HLH are variable and non-specific, hepatobiliary dysfunction, particularly a cholestatic pattern, may be underrecognized in the spectrum of HLH symptoms. Despite its rarity, HLH should remain a differential diagnosis in patients presenting with systemic symptoms, cytopenias and hepatobiliary dysfunction. In both cases, elevated liver enzymes either preceded or paralleled signs of hyperinflammation, highlighting that hepatobiliary dysfunction can serve as an early indicator for the immune dysregulation occurring in HLH.