PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonyms: familial non-haemolytic hyperbilirubinaemia, constitutional hepatic dysfunction
Gilbert's syndrome is usually an autosomal recessive disorder and is a common cause of unconjugated hyperbilirubinaemia. There have been some reports of heterozygous cases, mainly within Asian populations.
It was first described in 1901 by Nicolas Augustin Gilbert.
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Gilbert's syndrome affects 5-10% of people in Western Europe. The worldwide prevalence of Gilbert's syndrome varies considerably depending on which diagnostic criteria are used. Men are more commonly affected than women.
However, many cases remain undiagnosed so true prevalence is unknown.
Patients with Gilbert's syndrome have a defect in the gene that encodes for glucuronyltransferase, which results in a 60-70% reduction in the liver's ability to conjugate bilirubin.
It is a benign condition and it is not associated with liver disease.
Gilbert's syndrome is characterised by unconjugated hyperbilirubinemia, no evidence of haemolysis, normal liver enzyme levels and no evidence of liver disease.
It is usually diagnosed around puberty, and aggravated by intercurrent illness, stress, fasting or after administration of certain drugs.
The increase in serum concentrations of unconjugated bilirubin can lead to intermittent episodes of non-pruritic jaundice, which can be precipitated by fasting, infections, dehydration, surgery, physical exertion and lack of sleep. Symptoms, including tiredness, that occur during episodes of jaundice are caused by the precipitating factor and do not result directly from Gilbert's syndrome.
It can remain unnoticed for many years, but usually presents in adolescence with:
- Intermittent jaundice noticed after fasting, lack of sleep, vigorous exercise or during an intercurrent illness.
- Exposure to certain medications which may precipitate jaundice - eg, chemotherapy. Adverse effects of anticancer agents have been observed in Gilbert's syndrome patients due to reduced drug or bilirubin glucuronidation.
If there is any clinical concern, then discussion with a gastroenterologist or hepatologist is advisable. Some centres offer genetic testing to confirm Gilbert's syndrome if there is any doubt.
FBC shows normal reticulocyte count - to distinguish from haemolysis. Gilbert's syndrome patients tend to have total serum bilirubin levels from 17-100 μmol/L.
- Other LFTs (including lactate dehydrogenase) and liver biopsy are normal, but the latter should rarely be required.
- There is no bilirubin and subnormal amounts of urobilinogen in the urine.
This is excellent. No treatment is required and life expectancy is normal.
The following drugs should be avoided if alternatives are available:
- Atazanavir and indinavir (used for the treatment of HIV infection).
- Irinotecan (used for the treatment of advanced bowel cancer).
This is because drugs that inhibit glucuronyltransferase activity, such as gemfibrozil, and the protease inhibitors atazanavir and indinavir, can trigger episodes of jaundice.
Bilirubin is an endogenous antioxidant. Gilbert's syndrome may actually reduce the risk of various age-related diseases because of the antioxidant properties of bilirubin. Interestingly, one recent study has found that mortality rates observed for people with Gilbert's syndrome in the general population were shown to be almost half those of people without evidence of Gilbert's syndrome.
Further reading & references
- Gilbert's syndrome; NICE CKS, September 2010
- Action on Gilbert's Syndrome
- British Liver Trust
- Children's Liver Disease Foundation
- Claridge LC, Armstrong MJ, Booth C, et al; Gilbert's syndrome. BMJ. 2011 Apr 19;342:d2293. doi: 10.1136/bmj.d2293.
- Sticova E, Jirsa M; New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol. 2013 Oct 14;19(38):6398-6407.
- Rawa K, Adamowicz-Salach A, Matysiak M, et al; Coexistence of Gilbert syndrome with hereditary haemolytic anaemias. J Clin Pathol. 2012 Jul;65(7):663-5. doi: 10.1136/jclinpath-2011-200580. Epub 2012 May 3.
- Ehmer U, Kalthoff S, Fakundiny B, et al; Gilbert syndrome redefined: a complex genetic haplotype influences the regulation of glucuronidation. Hepatology. 2012 Jun;55(6):1912-21. doi: 10.1002/hep.25561. Epub 2012 Apr 23.
- Maruhashi T, Soga J, Fujimura N, et al; Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012 Jul 31;126(5):598-603. doi: 10.1161/CIRCULATIONAHA.112.105775. Epub 2012 Jul 6.
- Horsfall LJ, Nazareth I, Pereira SP, et al; Gilbert's syndrome and the risk of death: a population-based cohort study. J Gastroenterol Hepatol. 2013 Oct;28(10):1643-7. doi: 10.1111/jgh.12279.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Hayley Willacy
Dr Louise Newson
Dr Adrian Bonsall