Case Presentation: A 35-year-old male with a history of chronic alcohol use disorder, tobacco use, and malnutrition presented to the emergency department with a few days of yellow discoloration of the eyes. He denied fevers, headache, chest pain, shortness of breath, abdominal pain, nausea, vomiting, dark or bloody stools, or urinary pain. He drank two tall beers and 2-4 shots of liquor daily. The physical exam revealed stable vital signs. He appeared lethargic and had diffuse skin jaundice. There was no distention or tenderness on the abdominal exam, and no asterixis was noted. Laboratory work showed hemoglobin 4.8 g/dl, mean corpuscular volume 102.3 fL, platelet count 126×109/L, haptoglobin < 10 mg/dl, lactate dehydrogenase (LDH) 818 IU/L, and white blood cell count (WBC) 11.57 10E9/L. The Direct Coombs test was negative. The prothrombin time was 13.3 sec, while the international normalized ratio (INR) was 1.17. The metabolic panel showed sodium of 125 mmol/L, potassium of 2.4 mmol/L, bicarbonate of 18 mmol/L, creatinine 0.47 mg/dL, total bilirubin 22.0 mg/dL, direct bilirubin 17.0 mg/dL, alkaline phosphate 686 IU/L, alanine aminotransferase (ALT) 78 IU/L, and aspartate aminotransferase (AST) 309 IU/L. The lipid panel revealed total cholesterol 931 mg/dL, triglycerides 401 mg/dL, and high-density lipoprotein (HDL) 4 mg/dL. Low-density lipoprotein (LDL) could not be calculated due to an ethanol level of 316 mg/dL. Screening for Hepatitis A, B, C, and HIV was negative. Additional tests for acetaminophen, serum copper, and ammonia were all within normal limits. Computed tomography (CT) of the abdomen and pelvis revealed significant hepatomegaly and hepatic steatosis. The patient was treated conservatively with IV fluids and electrolyte replacement. He was placed on a phenobarbital taper, CIWA protocol, and further counseled on alcohol abstinence. He received two packed red blood cell transfusions. Upper endoscopy showed pre-pyloric gastropathy. Proton pump inhibitor therapy was initiated. At discharge, his total and direct bilirubin, lipid panel, and hepatic function tests had improved. Outpatient follow-up with gastroenterology and primary care were scheduled.
Discussion: Alcohol use can lead to macrocytic anemia, alcoholic hepatitis, and cirrhosis. This case highlights Zieve Syndrome (ZS), a rare complication of heavy alcohol use characterized by hemolysis, jaundice, and hyperlipidemia[1,2,3]. Hyperlipidemia in ZS is transient, resolving within weeks, but atypical presentations with normal lipid levels exist [2]. The pathophysiology is unclear but may involve lipid accumulation in red blood cell membranes, glutathione enzyme destabilization, and fat mobilization from a fatty liver or dysregulated serum lipids due to pancreatic damage [3,4]. Differentiating ZS from alcoholic hepatitis is critical, as misdiagnosis can lead to harmful glucocorticoid use, increasing morbidity and infection risk [5,6]. Symptoms typically improve with alcohol abstinence and conservative therapy, though plasmapheresis may be required in severe cases [7].
Conclusions: Zieve syndrome is an under-recognized yet clinically significant complication of chronic alcohol use, defined by the triad of Coombs-negative hemolysis, cholestatic jaundice, and hyperlipidemia. This case highlights the necessity for heightened clinical awareness of Zieve syndrome, particularly among patients with a history of heavy alcohol use, to avoid unnecessary and potentially harmful interventions.