Abstract Introduction Fulminant hepatic failure (FHF) is a rapidly progressive and life-threatening condition characterized by acute hepatic dysfunction and encephalopathy in patients without preexisting liver disease. When accompanied by severe lactic acidosis and multiorgan failure, determining the underlying cause is critical yet challenging, with a broad differential encompassing infectious, autoimmune, metabolic, and toxin-mediated etiologies. Case Presentation A 62-year-old man with hypertension and alcohol use disorder presented with two weeks of fever, anorexia, nausea, and watery diarrhea following shellfish consumption. Initial laboratory studies showed AST 101 U/L, ALT 101 U/L, direct bilirubin 3.5 mg/dL, INR 1.5, and lactate 4.6 mmol/L. Imaging revealed chronic right hydronephrosis and incidental pancreatic duct dilation without biliary obstruction. Infectious, autoimmune, and metabolic workups were unremarkable, except for Klebsiella pneumoniae growth in urine culture.He was treated with ceftriaxone for presumed urinary infection. By hospital day 4, his condition worsened with persistent fever, leukocytosis, tachypnea, metabolic acidosis, and hypoglycemia. Broad-spectrum antibiotics (meropenem, doxycycline, vancomycin) and N-acetylcysteine were initiated for suspected fulminant hepatic failure. AST and ALT rose dramatically to 5,633 and 1,223 U/L, respectively; direct bilirubin surged to 12.9 mg/dL, INR to 4.8, and lactate exceeded 17 mmol/L. Despite escalation of care, the patient developed anuric acute kidney injury requiring CRRT and progressive respiratory failure necessitating intubation. He succumbed to refractory shock and multiorgan failure two days later.Autopsy revealed hepatomegaly, splenomegaly, and diffuse tissue injury. Liver histology demonstrated marked sinusoidal dilatation with hemophagocytic macrophages and lymphohistiocytic infiltration of portal tracts, while bone marrow confirmed hemophagocytosis—findings diagnostic of hemophagocytic lymphohistiocytosis (HLH). Markedly elevated ferritin and soluble CD25 levels further supported the diagnosis. Discussion HLH is a rapidly progressive hyperinflammatory syndrome that can mimic severe sepsis or hepatic failure. In adults, secondary HLH most often arises from infections, malignancies, or autoimmune disorders. In this case, the likely trigger was an infectious process, given the recent febrile illness, gastrointestinal symptoms, and Klebsiella pneumoniae infection. Diagnosis relies on clinical and histopathologic findings, including hemophagocytosis, hyperferritinemia, and elevated soluble CD25. Although liver injury is common in HLH, progression to acute liver failure with multiorgan dysfunction represents a particularly severe and often fatal manifestation. Clinicians should maintain a high index of suspicion for HLH in patients with unexplained hepatic failure, fever, cytopenias, and elevated inflammatory markers. Early recognition and prompt initiation of HLH-directed therapy may improve survival, though prognosis remains poor once fulminant hepatic failure develops. This abstract is funded by: None
Liu et al. (2026) studied this question.