What is Gilbert's syndrome?
Bilirubin is bound (conjugated) to uridine diphosphate-glucuronic acid in the liver before being secreted into bile. In Gilbert's syndrome, an inherited genetic defect reduces the production of the enzyme responsible for conjugation. The ability to conjugate bilirubin is reduced by 60-70 per cent causing the serum level of unconjugated bilirubin to increase above the normal upper limit.
It is estimated that 2-10 per cent of the general population have Gilbert's syndrome but many cases remain undiagnosed. It is a common cause of isolated unconjugated hyperbilirubinemia.
When should I suspect Gilbert's syndrome?
Suspect Gilbert's syndrome if a person has an incidental finding of an increased serum bilirubin level, typically not exceeding 68-85 micromol/L, with otherwise normal LFTs, or a single episode (or intermittent episodes) of mild jaundice without clinical evidence of liver disease, and associated with heavy physical exertion, fasting, surgery, dehydration, infectious illness, alcohol ingestion or lack of sleep.
What investigations should I do?
If the bilirubin level is less than three times the upper limit and is predominantly unconjugated (more than 70 per cent), recheck conjugated and unconjugated bilirubin levels in one to three months. If there is no increase in unconjugated bilirubin, no further tests are needed.
If unconjugated bilirubin is increasing, exclude haemolysis-request serum haptoglobin, lactate dehydrogenase, FBC with reticulocyte count, blood film and Coombs' test.
If the bilirubin level is more than three times the upper limit of normal, exclude haemolysis.
How do I make a diagnosis?
Gilbert's syndrome can be diagnosed when the person has unconjugated hyperbilirubinemia, no evidence of haemolysis, normal liver enzyme levels and no evidence of liver disease.
If there is any clinical concern, discuss with a gastroenterologist or hepatologist. Some centres offer genetic testing to confirm Gilbert's syndrome if there is any doubt.
How should I manage Gilbert's syndrome?
Reassure the patient that no treatment is necessary and that Gilbert's syndrome does not cause chronic liver disease.
Episodes of jaundice are self-limiting. Paracetamol is considered safe to use.
These recommendations are based on expert opinion found in review articles and a textbook and the opinion of CKS expert reviewers.
1. Hirschfield GM, Alexander GJ. Gilbert's syndrome: an overview for clinical biochemists. Ann Clin Biochem 2006; 43(Pt 5): 340-3.
2. Smellie S W, Ryder SD. Cases in primary care laboratory medicine: biochemical 'liver function tests'. BMJ 2006; 333(7566): 481-3.
3. Thompson, RPH. Jaundice. In: Warrell DA, Cox TM & Firth JD (Eds.) Oxford textbook of medicine 2010. 5th edn. Oxford, Oxford University Press.