What is the management and treatment of Gilbert syndrome?

From the Guidelines

Gilbert syndrome typically requires no specific treatment as it is a benign, inherited condition characterized by mild, unconjugated hyperbilirubinemia. Most individuals with Gilbert syndrome remain asymptomatic and can lead normal lives without any intervention. Management primarily involves patient education about the benign nature of the condition and reassurance that it does not lead to liver damage or other health complications. During times of increased bilirubin levels, which may occur during fasting, illness, stress, or physical exertion, patients may experience mild jaundice or fatigue. These episodes can be managed by maintaining adequate hydration, eating regular meals, and avoiding prolonged fasting. No medications are routinely prescribed for Gilbert syndrome. However, patients should be aware that certain medications metabolized by the UGT1A1 enzyme (the enzyme deficient in Gilbert syndrome) may need dosage adjustments, including irinotecan (a chemotherapy drug) 1. Patients should inform healthcare providers about their condition when prescribed new medications. The underlying mechanism of Gilbert syndrome involves a genetic variation in the UGT1A1 gene, resulting in reduced activity of the enzyme responsible for conjugating bilirubin, leading to mildly elevated unconjugated bilirubin levels in the blood.

Some key points to consider in the management of Gilbert syndrome include:

• Measurement of total and direct bilirubin is recommended to help identify patients with indirect hyperbilirubinemia due to Gilbert's syndrome or hemolysis versus liver injury 1.
• For patients with Gilbert’s syndrome, total bilirubin levels can fluctuate significantly and therefore direct bilirubin should be used for decision making 1.
• Patients with Gilbert syndrome can fast Ramadan with regular follow up of their bilirubin level 1.
• It is essential to rule out other liver conditions, such as hepatocellular carcinoma, through alpha-fetoprotein tumor marker testing 1.

In terms of monitoring and evaluation, patients with Gilbert syndrome should have their liver function tests, including ALT, AST, and bilirubin levels, monitored regularly, especially when taking medications that may affect the liver 1. The most recent and highest quality study recommends that patients with Gilbert syndrome should be managed with a focus on patient education, reassurance, and monitoring of liver function tests 1.

From the Research

Management and Treatment of Gilbert Syndrome

The management and treatment of Gilbert syndrome are primarily focused on reassurance and monitoring, as it is a benign condition.

• The clinical diagnosis of Gilbert's syndrome can be established with relative certainty if the patients have a mild hyperbilirubinemia with a high fraction of unconjugated bilirubin, normal values of liver enzymes, and no overt signs of hemolysis 2.
• Liver biopsy is not mandatory for diagnosis 2.
• According to recent studies, individuals with Gilbert's syndrome may benefit from the mild hyperbilirubinemia and are actually protected from the development of a wide variety of diseases 3.
• The syndrome is almost certainly part of a spectrum which includes the Crigler-Najjar syndromes; molecular biology data suggests that there is an absence of one (or even more) GT isoenzymes in these disorders 4.
• Despite the complicated pathogenesis of Gilbert's syndrome, management remains simply reassurance alone 4.
• It is crucial to establish a correct diagnosis and differentiate this syndrome from serious disorders of the liver tissue 5.

Diagnostic Tests

• The reduced caloric intake test and phenobarbital treatment seem to have low diagnostic specificity in Gilbert's syndrome when the differential diagnosis is that of hepatitis 2.
• Genetic testing may be necessary in some cases to confirm the diagnosis 6.
• The fraction of plasma unconjugated bilirubin of total bilirubin was significantly different in all three groups examined (Gilbert's syndrome, acute hepatitis, and normal subjects) 2.

Prognosis and Complications

• Gilbert's syndrome is considered as a rather benign disorder without necessity of any therapeutic intervention 5.
• Strong antioxidant effects of bilirubin were demonstrated in numerous studies and the protective role of hyperbilirubinemia in the pathogenesis of various oxidative stress-mediated diseases was suggested 5.
• Individuals with Gilbert's syndrome may be protected from the development of a wide variety of diseases, such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases 3.