THE AVAILABILITY of elexacaftor–tezacaftor–ivacaftor (ETI) has been associated with a marked reduction in cystic fibrosis liver disease (CFLD) progression, according to a nationwide analysis. Researchers observed that people with cystic fibrosis (pwCF) receiving ETI faced a substantially lower risk of developing severe liver complications, including portal hypertension bleeding, decompensated cirrhosis, and liver transplantation.
Using data from more than 10,000 patients across the French National Hospital Discharge Database, investigators compared outcomes before and after ETI became available in December 2019. The study found that the overall incidence of CFLD progression dropped from 25.4 per 1,000 person-years prior to ETI to just 1.2 per 1,000 person-years after its introduction. This translated to a 72 percent lower risk of severe liver complications during the ETI era.
Mortality rates and the need for lung transplantation also declined significantly following the rollout of ETI. Importantly, there was no observed increase in acute liver failure risk, alleviating concerns regarding potential hepatotoxicity. Patients in the ETI era also lived longer, with age at death shifting upward compared with the pre-ETI period.
While the findings indicate a strong temporal association between ETI introduction and improved liver-related outcomes, the authors caution that unmeasured confounders and parallel improvements in cystic fibrosis care may have contributed. Nonetheless, these results reinforce current guidance that cystic fibrosis–related liver disease should not be viewed as a contraindication for ETI therapy.
The data provide compelling evidence that ETI not only improves pulmonary outcomes but may also alter the course of extra-pulmonary manifestations of cystic fibrosis, particularly progressive liver disease. Further research will be needed to confirm causality and clarify the biological mechanisms driving these improvements.
Reference:
Mouliade C et al. Cystic Fibrosis Liver Disease Progression in the Era of Elexacaftor-Tezacaftor-Ivacaftor. JHEP Reports. 2025; doi:10.1016/j.jhepr.2025.101512
