S5497 Liver Caught in the Storm: A Relapsing Case of HLH-Associated Severe Acute Liver Injury

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome characterized by uncontrolled cytokine release and multi-organ dysfunction. We present a challenging case of acute liver injury in a patient with relapsing HLH. Case Description/Methods: A 72-year-old woman presented with fevers, jaundice and pancytopenia. Initial labs revealed aspartate aminotransferase (AST) 1361 U/L, alanine aminotransferase (ALT) 587 U/L and total bilirubin (TB) 17.8 mg/dL and alkaline phosphatase 429 U/L. Ferritin was markedly elevated at 11,221 ng/mL. Imaging showed splenomegaly, and her soluble CD25 level was 35,000 U/mL. Liver biopsy demonstrated features consistent with HLH. She was treated with etoposide and dexamethasone with improvement of symptoms and normalization of liver enzymes. Four months later, she returned with arthralgias, myalgias and recurrent elevation of liver enzymes with AST 1554 U/L, ALT >3500 U/L and TB 5.9 mg/dL. Repeat liver biopsy demonstrated small clusters of histiocytes and portal/lobular changes consistent with HLH relapse. She was retreated with etoposide, dexamethasone and cyclosporine with resolution of symptoms and biochemical improvement. Maintenance therapy was initiated with cyclosporine, dexamethasone and etoposide. However, one month later she presented with worsening liver tests (AST 1547 U/L, ALT 2316 U/L, TB 16 mg/dL), developed septic shock secondary from E. coli bacteremia, and passed away during the hospitalization. Discussion: Liver involvement in HLH is multifactorial, driven by cytokine-mediated injury, hemophagocytosis, and systemic inflammation. This case highlights the diagnostic and therapeutic complexities of HLH with liver involvement. The patient met 6 of the 8 diagnostic criteria, including fever >38.5°C, splenomegaly, cytopenias in ≥2 cell lines, elevated ferritin, hypertriglyceridemia, and elevated soluble CD25. Liver biopsy revealed classic features of HLH, including histiocytic infiltrates and portal tract injury. Despite initial improvement with treatment, her subsequent relapses and eventual death emphasize the aggressive nature of HLH and the challenges of long-term management. This case underscores the importance of early recognition, prompt intervention, and continued investigation into effective maintenance strategies, particularly in older patients.