Abstract
Zieve's syndrome is a rare and reversible cause of hemolytic anemia classically defined by the triad of hemolytic anemia, hyperbilirubinemia, and transient hyperlipidemia in the setting of recent heavy alcohol use. It is frequently underrecognized, particularly in patients with alcohol-associated liver cirrhosis, where anemia is often attributed to gastrointestinal bleeding, hypersplenism, or bone marrow dysfunction. This syndrome represents an important diagnostic pitfall because transfusion-refractory anemia may be misattributed to gastrointestinal bleeding or autoimmune hemolytic anemia, leading to unnecessary invasive procedures. We present a 48-year-old man with alcohol use disorder and decompensated alcohol-associated liver cirrhosis who presented with lethargy and severe, transfusion-refractory anemia. Despite multiple transfusions, his hemoglobin demonstrated minimal and transient improvement. An extensive evaluation, including esophagogastroduodenoscopy, colonoscopy, direct antiglobulin testing (DAT), and workup for inherited and acquired hemolytic disorders, excluded gastrointestinal bleeding, autoimmune hemolysis, and other causes of hemolysis. Laboratory findings demonstrated DAT-negative hemolytic anemia with marked hyperbilirubinemia and paradoxical hyperlipidemia, while bone marrow biopsy revealed erythroid hyperplasia without evidence of myelodysplasia. With supportive care and alcohol cessation, the patient's hemoglobin improved without further transfusion requirements. This case highlights Zieve's syndrome as an important diagnostic consideration in patients with alcohol-associated cirrhosis presenting with transfusion-refractory anemia, as early recognition can prevent unnecessary invasive procedures, and emphasizes alcohol cessation as the cornerstone of management.