Zieve's syndrome is a disorder that manifests with anemia, jaundice, and hyperlipidemia, in the setting of alcoholism and hepatic cirrhosis.
Zieve's syndrome is observed in suspected or known alcoholic patients and leads to the manifestation of transient jaundice due to acute hemolytic anemia and hyperlipidemia [1]. Individuals affected by the syndrome typically suffer from steatohepatitis as well.
Anemia is always present in the case of Zieve's syndrome and follows a hemolytic pathophysiological route, causing the appearance of jaundice. The symptoms such as fatigue and malaise may be seen in mild cases. A considerable number of patients, however, are affected by severe anemia, which is responsible for a profound set of symptoms, including tachycardia, tachypnea, and hypotension. Loss of consciousness and dizziness may be present due to the anemic condition of the patient in the Zieve's syndrome.
Pain in the right upper quadrant abdominal region is also a common symptom, leading to confusion between Zieve's syndrome and acute cholecystitis [2]. Patients have also reported myalgia, which occurs due to an increased serum viscosity, and retinal damage has also been observed, even though there may be no symptoms accompanying the latter [3] [4]. Some patients diagnosed with Zieve's syndrome present with intracranial hemorrhage, that has mainly been attributed to the increase in serum lipids, with this symptom being documented in only four cases [5].
The diagnosis of Zieve's syndrome may be difficult, due to the similarities with other conditions and due to the habit of alcoholism often being withheld by the patients. The primary aim is to distinguish the syndrome from other medical conditions, such as acute cholecystitis and acute alcoholic hepatitis.
The initial laboratory evaluation of any patient presenting with jaundice, signs of anemia and possibly upper right abdominal quadrant pain includes the following:
Distinguishing Zieve's syndrome from acute cholecystitis requires an initial thorough physical examination. Patients affected by the syndrome do not display a positive Murphy's sign and are typically afebrile, in contradistinction to acute cholecystitis. Furthermore, indirect serum bilirubin levels are profoundly elevated in Zieve's syndrome, amounting to over 5 mg/dL, whereas values between 2 and 5 mg/dL are expected in acute cholecystitis. A right upper quadrant ultrasonographic scan (RUQ US) or cholescintigraphy are also required: a lack of gallstones or pericholecystic fluid direct the diagnostic process towards Zieve's syndrome. These procedures, however, may render inconclusive results, such as gallbladder distention, findings which do not aid in the differential diagnosis of Zieve's syndrome and acute cholecystitis [6].
Zieve's syndrome also needs to be differentiated from acute alcoholic hepatitis. These two medical entities are distinguished, due to the fact that the former leads to hyperlipidemia in combination with hemolytic anemia, whereas the latter is characterized by a remarkable increase in transaminase levels (AST< 300 IU/mL), hyperbilirubinemia and a prolonged international normalized ratio (INR) [6]. Moreover, patients suffering from acute alcoholic hepatitis exhibit a steadily declining course, despite appropriate treatment, whereas Zieve's syndrome tends to regress, once the alcoholic trigger has been removed [6].
Given that Zieve's syndrome may also induce intracranial or retinal hemorrhage, fundoscopy and a complete neurological examination may be required [7]. Neurological deficits may indicate the need for further investigation.
Also, in the cases of individuals who have not yet been diagnosed with fatty liver disease or steatohepatitis, a liver biopsy will illustrate a fatty infiltration of the liver. In general, Zieve's syndrome must be considered as a possible pathology, when a patient with a history presents with indirect hyperbilirubinemia, a medical history of alcoholism and no other probable causes for the biochemical anomaly [8].