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Gilbert's disease

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Gilbert's disease is a benign, mildly symptomatic, non- haemolytic, unconjugated hyperbilirubinaemia in the absence of liver disease (1).

  • it is a common cause of isolated raised unconjugated bilirubin (2)
  • total plasma bilirubin can be as high as 80 mumol/l and mild intermittent jaundice does occur
  • inheritance pattern is probably autosomal recessive (3)
  • has been estimated that some 10-15% of the Western population suffers from Gilbert's syndrome

The main abnormality is decreased bilirubin conjugating capacity (4)

  • bilirubin-uridinediphosphate-glucuronosyltransferase (UGT1A1) is the only enzyme involved in the conjugation of bilirubin
    • in patients with Gilbert's syndrome, hepatic glucuronidation by UGT1A1 is reduced to about 30% of normal (1)
  • although Gilbert’s syndrome does not lead to progressive liver damage it has attracted attention regarding the pharmacogenetics of drug metabolism
    • apart from being the only physiological UGT capable of bilirubin glucuronidation, UGT1A1 also catalyzes the glucuronidation of 2-hydroxy-estrone and estradiol, and a number of therapeutic drugs such as ethinylestradiol, gemfibrozil, metabolites of irinotecan, simvastatin and buprenorphine
It is at least twice as common in men than in women (5)

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