From the Guidelines
Gilbert syndrome is a benign condition that does not require treatment, as it does not cause liver damage or serious health problems, and individuals with this condition have a normal life expectancy. This condition is characterized by elevated levels of unconjugated bilirubin in the blood, causing occasional mild jaundice, and is caused by a partial deficiency of the enzyme UGT1A1, which is responsible for processing bilirubin 1. Symptoms, when they occur, may include yellowing of the skin and eyes, fatigue, and abdominal discomfort, particularly during times of stress, illness, fasting, or physical exertion.
Key Considerations
- These episodes are temporary and resolve on their own, and maintaining good hydration, eating regular meals, and avoiding excessive alcohol can help minimize episodes.
- It's essential to inform healthcare providers about having Gilbert syndrome to avoid unnecessary testing when mild jaundice appears.
- Despite the elevated bilirubin levels, liver function tests are otherwise normal, and people with Gilbert syndrome have normal life expectancy.
Diagnostic Considerations
- Diagnosis is confirmed by calculating the amount of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin, in the absence of haemolysis 1.
- Genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase should be considered when the diagnosis is unclear 1.
Clinical Implications
- Patients with Gilbert syndrome may be enrolled in clinical trials, but it's crucial to accurately identify this condition to avoid misdiagnosis and unnecessary diagnostic testing or drug interruption 1.
- In clinical trials, particularly those involving cholestatic liver diseases, it's essential to distinguish between Gilbert syndrome and drug-induced liver injury (DILI) to ensure accurate causality assessment and patient management 1.
From the Research
Definition and Characteristics of Gilbert Syndrome
- Gilbert syndrome is a common autosomal dominant hereditary condition with incomplete penetrance, characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis 2.
- It is typically noticed as intermittent mild jaundice in adolescence, but can be potentiated by other prevailing conditions such as breast feeding, G-6-PD deficiency, thalassemia, spherocytosis, or cystic fibrosis 2.
- The most common genotype of Gilbert syndrome is the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1) 2.
Diagnosis of Gilbert Syndrome
- 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 3.
- Molecular genetic tests can now be performed when there is a diagnostic problem 2.
- 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 3.
Treatment and Management of Gilbert Syndrome
- No specific management is necessary as Gilbert syndrome is a benign condition 2.
- Phenobarbital treatment can significantly reduce the level of unconjugated serum bilirubin in patients with Gilbert's syndrome, but it is not a diagnostic criterion 3, 4.
- Patients with Gilbert syndrome should be educated about the condition, and periods of fasting, stress, and illness can worsen unconjugated hyperbilirubinemia, leading to complications 5.
Differential Diagnosis
- Gilbert syndrome should be differentiated from other conditions such as Crigler-Najjar syndrome type II, which is caused by mutations in the UGT1A1 gene resulting in severely reduced hepatic activity of UDP-glucoronyltransferase 5.
- Unconjugated bilirubin levels can be higher in Crigler-Najjar syndrome type II than in Gilbert syndrome, and patients with the former condition respond to phenobarbital therapy 5.