What is Gilbert syndrome and how is it managed?

From the Guidelines

Gilbert syndrome is a benign genetic liver disorder that requires no specific treatment, only lifestyle modifications to manage occasional mild jaundice and prevent triggers such as prolonged fasting, illness, and stress. This condition is characterized by elevated levels of unconjugated bilirubin in the blood, which can cause yellowing of the skin and eyes 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.

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

• Maintaining adequate hydration and eating regular meals to prevent episodes of jaundice
• Avoiding prolonged fasting, which can trigger episodes of jaundice 1
• Being aware of triggers such as illness, stress, and fasting, which can temporarily worsen symptoms
• Using caution with certain medications that affect liver function, though most medications are safe
• Moderate alcohol consumption, as excessive intake can exacerbate bilirubin levels

The condition occurs due to a genetic mutation affecting the UGT1A1 enzyme, which is responsible for conjugating bilirubin so it can be excreted 1. Despite occasional mild symptoms, people with Gilbert syndrome have a normal life expectancy and do not require regular medical monitoring beyond routine healthcare. It is also worth noting that fasting, such as during Ramadan, may initially increase plasma unconjugated bilirubin concentration, but this typically decreases to basal values by the end of the fasting period 1.

From the Research

What is Gilbert Syndrome

• Gilbert syndrome is a benign and inherited condition characterized by mild, lifelong, unconjugated hyperbilirubinaemia in the absence of haemolysis or evidence of liver disease 2.
• It is also known as benign hyperbilirubinaemia and is usually considered a physiological abnormality 3.
• The condition is characterized by a mild elevation of the systemic level of unconjugated bilirubin 3.

Causes and Pathophysiology

• The molecular basis of Gilbert syndrome is mutations in the TATA box upstream of the uridine diphosphoglucose glucuronyltransferase gene, leading to impaired bilirubin glucuronidation 2.
• This impairment results in a reduction in the ability to conjugate bilirubin, leading to an increase in unconjugated bilirubin levels in the blood 4.

Diagnosis

• The diagnosis of Gilbert 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 5.
• The rifampicin test can be used as a diagnostic test, with elevation of total serum bilirubin after rifampin above 2.4 mg/dL being 93.8% sensitive and 93.3% specific for the diagnosis of GS 6.
• The fasting test can also be used, but it may not be as specific as the rifampicin test, as it can cause an increase in unconjugated bilirubin levels in patients with chronic liver disease 4.

Management

• Gilbert syndrome is a benign condition and does not require specific treatment 2.
• Individuals with Gilbert syndrome may actually benefit from the mild hyperbilirubinaemia and are protected from the development of a wide variety of "diseases of civilisation" such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases 3.
• However, it is essential to distinguish Gilbert syndrome from other liver diseases, and a correct diagnosis can help avoid unnecessary investigations and treatments 5.