What is the prognosis of Gilbert syndrome?

Updated: May 21, 2019
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
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Gilbert syndrome is a common and benign condition. The bilirubin disposition may be regarded as falling within the range of normal biologic variation. The syndrome has no deleterious associations and an excellent prognosis, and affected persons can lead a normal lifestyle. As further confirmation of its benign nature, studies have reported excellent results in patients undergoing living-donor liver transplantation from donors with Gilbert syndrome. [50, 51]

Epidemiologic studies have reported an association between Gilbert syndrome, hyperbilirubinemia, and a reduced risk of cardiovascular disease. [52, 53, 54] The exact mechanism for this finding is unclear, but the antioxidant properties of bilirubin may be contributory in conjunction with heme oxygenase. (See the image below.) [55, 56, 57] Moreover, mildly elevated unconjugated bilirubin appears to be associated with reduced platelet activation-related thrombogenesis and inflammation in patients with Gilbert syndrome, which may play a role in protecting these individuals from cardiovascular mortality. [54]

Production of bilirubin. Production of bilirubin.

Clinicians need to be aware that patients with Gilbert syndrome may be at higher risk of developing toxicity from certain medications (eg, irinotecan) and protease inhibitors (eg, atazanavir, [58, 59] indinavir) that can inhibit UGT metabolism. [60] A study by Lankisch et al reported that the risk of severe hyperbilirubinemia with indinavir was associated with genetic variants of UGT1A3 and UGT1A7 genes in addition to Gilbert syndrome (UGT1A1*28). [61]

Kweekel et al reported that patients who were more likely to develop the side effects of irinotecan toxicity, such as life-threatening neutropenia and diarrhea, were more likely to have an underlying liver disease, hepatic conjugation disorders, or UGT1A1*28 genotype. [62] However, due to a lack of prospective data, the relationship between the UGT1A1 genotype and irinotecan toxicity remains unclear, although the irinotecan product label recommends reducing the irinotecan dose in patients with this genotype.

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