What are the standard of care, differential diagnoses, and workup for Gilbert's disease (a benign condition characterized by intermittent jaundice due to mildly elevated levels of unconjugated bilirubin)?

From the Guidelines

Gilbert syndrome is a benign condition characterized by mild unconjugated hyperbilirubinemia without liver disease, and the standard of care involves a comprehensive history and physical examination, followed by laboratory tests including complete blood count, liver function tests, and fractionated bilirubin levels to confirm the diagnosis. The differential diagnosis for Gilbert syndrome includes other causes of unconjugated hyperbilirubinemia such as hemolytic anemias, Crigler-Najjar syndrome, and drug-induced hyperbilirubinemia. The workup for Gilbert syndrome typically begins with a comprehensive history and physical examination, followed by laboratory tests including:

• Complete blood count
• Liver function tests
• Fractionated bilirubin levels Additional testing may include:
• Reticulocyte count
• Peripheral blood smear
• Hemoglobin electrophoresis to rule out hemolytic causes Genetic testing for UGT1A1 gene mutations, particularly the UGT1A1*28 variant, can confirm the diagnosis but is rarely necessary in clinical practice 1. The diagnosis of Gilbert's Syndrome should be determined by calculating the proportion of conjugated bilirubin which should be less than 20%‐30% of the total bilirubin 1. Provocative tests like fasting for 24-48 hours or administering phenobarbital are no longer routinely recommended. Gilbert syndrome requires no treatment as it's a benign condition without clinical consequences, and patients should be reassured about its benign nature. The condition results from reduced activity of the enzyme UDP-glucuronosyltransferase, which is responsible for bilirubin conjugation in the liver, leading to mildly elevated unconjugated bilirubin levels. In clinical practice, it is essential to differentiate Gilbert syndrome from other causes of jaundice, such as hepatitis, alcoholic liver disease, and blockage of the common bile duct, which may require prompt medical attention 1. The management of Gilbert syndrome is primarily focused on reassuring the patient and educating them about the benign nature of the condition, as well as monitoring for any potential complications or associated conditions 1.

From the Research

Standard of Care for Gilbert's Disease

• The standard of care for Gilbert's disease is mainly focused on reassurance and management of symptoms, as it is a benign condition 2.
• Patients with Gilbert's disease may experience intermittent episodes of jaundice, but they do not require specific treatment for the condition itself.

Differential Diagnoses for Gilbert's Disease

• Differential diagnoses for Gilbert's disease include other causes of hyperbilirubinemia, such as liver disease, hemolytic anemia, and other genetic disorders 3, 4.
• Hereditary spherocytosis, a genetic disorder that affects the production of red blood cells, can coexist with Gilbert's disease and cause more severe jaundice 3.
• Other conditions, such as alpha-1 antitrypsin deficiency, Wilson disease, and progressive familial intrahepatic cholestasis, can also cause liver disease and hyperbilirubinemia 4.

Workup for Gilbert's Disease

• The workup for Gilbert's disease typically involves laboratory tests to evaluate liver function and rule out other causes of hyperbilirubinemia 5, 4.
• Genetic testing may be used to confirm the diagnosis of Gilbert's disease, but its usefulness depends on various factors, including the prevalence and penetrance of the gene defect 2.
• Imaging studies and other diagnostic tests may be necessary to evaluate the underlying cause of jaundice and to rule out other conditions that may be causing hyperbilirubinemia 5.