Gilbert's syndrome leads to elevated bilirubin after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis

Pediatr Pulmonol. 2024 Apr;59(4):863-866. doi: 10.1002/ppul.26831. Epub 2024 Jan 5.

Abstract

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert's Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert's Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF.

Keywords: CFTR modulator; cystic fibrosis; elevated direct bilirubin; elexacaftor/tezacaftor/ivacaftor; gilbert's syndrome.

MeSH terms

  • Aminophenols / therapeutic use
  • Benzodioxoles / therapeutic use
  • Bilirubin
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / drug therapy
  • Gilbert Disease*
  • Humans
  • Indoles*
  • Mutation
  • Pyrazoles*
  • Pyridines*
  • Pyrrolidines*
  • Quinolones*
  • Syndrome

Substances

  • elexacaftor
  • ivacaftor
  • tezacaftor
  • Bilirubin
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Benzodioxoles
  • Aminophenols
  • Indoles
  • Pyrazoles
  • Pyridines
  • Pyrrolidines
  • Quinolones

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