What are the nonsurgical options for Gilbert syndrome?

Updated: May 21, 2019
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
  • Print
Answer

No therapy is necessary for patients with Gilbert syndrome. However, many therapeutic approaches have been used. As with Crigler-Najjar type II syndrome, phenobarbital has been shown to decrease bilirubin production. The most important aspect in the care of patients with Gilbert syndrome, however, is recognition of the disorder and its inconsequential nature.

Toxicity

Irinotecan toxicity in Gilbert syndrome is of some concern, however. As a result of a mutation in the UGT1A1 gene promoter, affected patients show reduced inactivation of the active topoisomerase inhibitor 7-ethyl-10-hydroxycampothecin (SN-38). Glucuronidation rates of the active metabolite SN-38 are significantly lower in people who are homozygous and heterozygous for the TA-TATAA variant allele than in those with the wild-type genotype (TATAA).

In patients with Gilbert or Crigler-Najjar syndrome, reduced glucuronidation of SN-38 leads to SN-38 toxicity and causes symptoms such as diarrhea. Preliminary results from clinical trials suggest that screening cancer patients for the UGT1A1 promoter polymorphism may reduce the prevalence of irinotecan toxicity. Until this evidence is available, caution is warranted before irinotecan is prescribed to this subset of patients.

Pharmacogenetics

The clinical relevance of pharmacogenetics in Gilbert syndrome has yet to be determined. Although impaired glucuronidation and excretion of certain drugs have been reported, such impairment has not resulted in any adverse clinical events, and the risk probably remains more theoretical than real. [60, 61]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!